Compositions, apparatus, systems, and methods for resolving electronic excited states

ABSTRACT

The present disclosure relates, according to some embodiments, to molecules, including conjugated fused polycyclic molecules, that may receive excited state energy from other molecules (e.g., light-absorbing molecules) or directly from the irradiation sources. According to some embodiments, the disclosure relates to molecules, including conjugated fused polycyclic molecules, that may resolve (e.g., quench, dissipate) excited state energy, normally by way of releasing it as heat. (e.g., as heat). Conjugated fused polycyclic molecules of various structures are disclosed including Formula III: 
     
       
         
         
             
             
         
       
     
     The disclosure further relates to methods of use and/or therapy using molecules of Formulas I, II, and/or III.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a division of U.S. application Ser. No. 13/963,865filed Aug. 9, 2013. U.S. application Ser. No. 13/963,865 is acontinuation-in-part of U.S. application Ser. No. 13/588,662 filed Aug.17, 2012, a continuation-in-part of International PCT Application No.PCT/US12/67519 filed Dec. 3, 2012 and a continuation-in-part of U.S.application Ser. No. 13/805,168 filed Dec. 18, 2012. U.S. applicationSer. No. 13/963,865 also claims priority to U.S. Provisional PatentApplication No. 61/681,916, filed on Aug. 10, 2012. The contents of allof the above applications are hereby incorporated in their entirety byreference.

FIELD OF THE DISCLOSURE

The present disclosure relates, in some embodiments, to molecules,including conjugated fused polycyclic molecules, that may receiveexcited state energy from other molecules (e.g., light-absorbingmolecules) or directly from the irradiation sources. According to someembodiments, the present disclosure relates to molecules, includingconjugated fused polycyclic molecules, that may quench, dissipate,and/or otherwise resolve excited state energy, normally by way ofreleasing it as heat. (e.g., as heat).

BACKGROUND OF THE DISCLOSURE

Irradiation energy can have a detrimental impact on exposed substancesand organisms. When a molecule absorbs light, the absorbed photon maypropel an electron from a lower energy orbital (e.g., ground state) to ahigher energy orbital (e.g., excited state). A molecule with an excitedelectron may be unstable; it may readily react with surroundingmolecules to release the excited state energy and return its electron toa lower energy state. The manner in which the excited energy state isresolved may have a substantial impact on the ultimate effect of theabsorption event. For example, photosynthetic organisms can harvest theabsorbed energy and convert it to usable chemical energy. In many cases,however, excited state energy is resolved in less productive and evendetrimental ways. For example, reactive oxygen species and otherreactive free radicals may be formed. These highly reactive speciesoften react by oxidizing one or more surrounding molecules. Theresulting damage may vary in kind and extent. Other consequences ofreactions resulted from excited state molecule include: pigmentmolecules bleaching, polymers degradation, DNA mutation. plasmamembranes damage, and ectopically and/or deleteriously activation ofintracellular signaling.

SUMMARY

Accordingly, a need has arisen for improved compositions, apparatus,systems, and methods for resolving electronic excited states. Thepresent disclosure relates, according to some embodiments, tocompositions, apparatus, systems, and methods for resolving electronicexcited states (e.g., quenching singlet and triplet electronic excitedstates). For example, a method may comprise resolving an excited stateof a chromophore (e.g., a chromophore commonly found in polymericmaterials and in organic colorants) by contacting the chromophore and aconjugated fused tricyclic compound (e.g., a conjugated fused tricycliccompound having at least two electron withdrawing group. Upon contact, atricyclic compound may quench singlet and/or triplet excited states of achromophore by accepting an electron from the chromophore, therebyreturning the chromophore back to the ground state, in some embodiments.A molecule (e.g., photolabile chromophore moiety) may reach an excitedstate when illuminated by visible and/or UV radiation at a wavelength inthe range of about 290 to about 800 nm, commonly found in sunlight. Whenan excited molecule (e.g., an excited chromophore in polymeric moleculeand organic colorant) interacts with a conjugated fused tricycliccompound having at least two electron withdrawing groups, the excitedmolecule is returned to the ground state and photostabilized. Further,when an excited molecule interacts with a conjugated fused tricycliccompound having at least two electron withdrawing groups, the excitedstate of the molecule is effectively quenched substantially before itcan react interact with oxygen, preventing the generation of reactiveoxygen species.

The present disclosure relates, in some embodiments, to conjugated fusedpolycyclic molecules and compositions for resolving an electronicallyexcited state. A composition may comprise, for example, a photoactivemolecule and/or a photosensitizer. A composition may further comprise aconjugated fused polycyclic molecule having a structure according toFormula I:

wherein

-   -   R₁ independently may be nitrile, C(O)R₃, C(O)N(R₄)R₅, C(O)—S—R₆,        or fused aryl,    -   R₂ independently may be nitrile, C(O)R₇C(O)N(R₈)R₉, C(O)—S—R₁₀,        or fused aryl,    -   R₃, R₄, R₅, R₆, R₇, R₈, R₉, and R₁₀ each independently may be H,        aryl, substituted aryl, fused aryl, alkyl, substituted alkyl, or        branched alkyl,    -   D₁ independently may be H, hydroxyl, or R₁₁,    -   D₂ independently may be H, hydroxyl, or R₁₂, and    -   R₁₁ and R₁₂ each independently may be H, alkyl, heteroalkyl,        alkoxyl, heteroalkoxyl, aryl, heteroaryl, or fused aryl,        provided that    -   R₁ and R₂ are not both nitrile,    -   R₁ and R₂ are not fused to each other,    -   R₁₁ and R₁₂ do not comprise azo,    -   the fused tricyclic moiety defined by rings X, Y, and Z is the        only tricyclic moiety in the molecule, and/or    -   D₁ and D₂ are not fused to each other.        In some embodiments, a conjugated fused polycyclic molecule        according to Formula I may be configured (a) to resolve at least        one excited state of a photoactive molecule substantially        without observable photochemical reactions, (b) to resolve at        least one excited state of a photoactive molecule substantially        non-radiatively, or (c) to resolve at least one excited state of        a photoactive molecule substantially without observable        photochemical reactions and substantially non-radiatively. In        some embodiments, a conjugated fused polycyclic molecule        according to Formula I may be configured (a) to resolve at least        one excited state of a photosensitizer molecule substantially        without observable photosensitization reactions, (b) to resolve        at least one excited state of a photosensitizer molecule        substantially non-radiatively, or (c) to resolve at least one        excited state of a photosensitizer molecule substantially        without observable photosensitization reactions and        substantially non-radiatively.

According to some embodiments, R₁ and R₂ may be different from eachother. D₁ and D₂ may be hydrogen, in some embodiments. R₃, R₄, R₅, R₆,R₇, R₈, R₉, and R₁₀, in some embodiments, may be each independently analkyl group having from about 1 to about 30 carbon atoms. In someembodiments, R₁ and R₂ are both nitrile and, in some embodiments,neither R₁ nor R₂ is nitrile. A conjugated fused polycyclic molecule ofFormula I may comprise no more than 4 rings fused to each other and/orno more than 6 rings total, according to some embodiments.

In some embodiments, a composition may comprise a conjugated fusedpolycyclic molecule having a structure according to Formula II:

wherein

-   -   A₁ independently may be carbonyl, C═C(R₁₃)R₁₄, O, S, S═O,        S(O)═O, C═S,    -   R₁₃ independently may be nitrile, C(O)OR₁₅, C(O)R₁₆,        C(O)N(R_(n))R₁₈, C(O)—S—R₁₉, aryl, substituted or fused aryl,    -   R₁₄ independently may be nitrile, C(O)OR₂₀, C(O)R₂₁,        C(O)N(R₂₂)R₂₃, C(O)—S—R₂₄, aryl, substituted or fused aryl,    -   R₁₅, R₁₆, R₁₇, R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, and R₂₄ each        independently may be aryl, substituted aryl, fused aryl, alkyl,        substituted alkyl, or branched alkyl,    -   A₂ independently may be carbonyl, C═C(R_(n))R₁₄, O, S, S═O,        S(O)═O, C═S,    -   D₃ independently may be H, hydroxyl, or R₂₅,    -   D₄ independently may be H, hydroxyl, or R₂₆, and    -   R₂₅ and R₂₆ each independently may be alkyl, heteroalkyl,        alkoxyl, heteroalkoxyl, aryl, heteroaryl, or fused aryl,        provided that    -   at least one of A₁ and A₂ is C═C(R₁₃)R₁₄,    -   if neither A₁ nor A₂ is S, for each C═C(R₁₃)R₁₄, no more than        one of R₁₃ and R₁₄ is nitrile (e.g., if both A₁ and A₂ are        C═C(R₁₃)R₁₄, no more than one of R₁₃ and R₁₄ of the A₁ group may        be nitrile and no more than one of R_(n) and R₁₄ of the A₂ group        may be nitrile), and    -   if either A₁ nor A₂ is O, for each C═C(R₁₃)R₁₄, no more than one        of R₁₃ and R₁₄ is C(O)OR_(15/20) (e.g., R₁₄ cannot be C(O)OR₂₀        if A₂ is O and R₁₃ is C(O)OR₁₅).        In some embodiments, a conjugated fused polycyclic molecule        according to Formula II may be configured (a) to resolve at        least one excited state of a photoactive molecule substantially        without observable photochemical reactions, (b) to resolve at        least one excited state of a photoactive molecule substantially        non-radiatively, or (c) to resolve at least one excited state of        a photoactive molecule substantially without observable        photochemical reactions and substantially non-radiatively. In        some embodiments, a conjugated fused polycyclic molecule        according to Formula II may be configured (a) to resolve at        least one excited state of a photosensitizer molecule        substantially without observable photosensitization        reactions, (b) to resolve at least one excited state of a        photosensitizer molecule substantially non-radiatively, or (c)        to resolve at least one excited state of a photosensitizer        molecule substantially without observable photosensitization        reactions and substantially non-radiatively.

According to some embodiments, R₁₃ and R₁₄ may be different from eachother. D₃ and D₄ may be hydrogen, in some embodiments. R₁₅, R₁₆, R₁₇,R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, and R₂₄, in some embodiments, may be eachindependently an alkyl group having from about 1 to about 30 carbonatoms. In some embodiments, R₁₃ and R₁₄ are both nitrile and, in someembodiments, neither R₁₃ nor R₁₄ is nitrile. A conjugated fusedpolycyclic molecule of Formula II may comprise no more than 4 ringsfused to each other and/or no more than 6 rings total, according to someembodiments.

In some embodiments, a composition may comprise a conjugated fusedpolycyclic molecule having a structure according to Formula III:

wherein

-   -   m and n each independently may be 0, 1, 2, 3, or 4,    -   r and s each may be 0 or 1,    -   A₃ and A₄ each independently may be carbonyl, C═C(R₂₇)R₂₈, O, S,        S═O, S(O)═O, or C═S,    -   R₂₇ independently may be nitrile, C(O)OR₂₉, C(O)R₃₀,        C(O)N(R₃₁)R₃₂, C(O)—S—R₃₃, C(O)—O—S—R₃₄, C═CHR₃₅, N(R₃₆)₃ ⁺, F,        Cl, Br, I, CF₃, CCl₃, NO₂, aryl, substituted aryl, or fused        aryl,    -   R₂₈ independently may be nitrile, C(O)OR₃₇, C(O)R₃₈,        C(O)N(R₃₉)R₄₀, C(O)—S—R₄₁, C(O)—O—S—R₄₂, C═CHR₄₃, N(R₄₄)₃ ⁺, F,        Cl, Br, I, CF₃, CCl₃, NO₂, aryl, substituted aryl, or fused        aryl,    -   R₂₉ and R₃₇ each independently may be H, alkyl, cycloalkyl,        alkenyl, cycloalkenyl, alkynyl, aryl, substituted aryl, or fused        aryl,    -   R₃₀, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, R₃₈, R₃₉, R₄₀, R₄₁, R₄₂, and R₄₃        each independently may be H, alkyl, cycloalkyl, alkenyl,        cycloalkenyl, alkynyl, or aryl, substituted aryl, or fused aryl,        alkyl, substituted alkyl, or branched alkyl,    -   R₃₆ and R each independently may be H or C₁-C₆ alkyl, and    -   D₅ and D₆ may be independently R₂₇, R₂₈, heteroaryl, hydroxyl,        alkyl, or alkoxyl, provided that    -   r+s≧1, and    -   at least one of A₃ and A₄ is C═C(R₂₇)R₂₈.        In some embodiments, a conjugated fused polycyclic molecule        according to Formula III may be configured (a) to resolve at        least one excited state of a photoactive molecule substantially        without observable photochemical reactions, (b) to resolve at        least one excited state of a photoactive molecule substantially        non-radiatively, or (c) to resolve at least one excited state of        a photoactive molecule substantially without observable        photochemical reactions and substantially non-radiatively. In        some embodiments, a conjugated fused polycyclic molecule        according to Formula III may be configured (a) to resolve at        least one excited state of a photosensitizer molecule        substantially without observable photosensitization        reactions, (b) to resolve at least one excited state of a        photosensitizer molecule substantially non-radiatively, or (c)        to resolve at least one excited state of a photosensitizer        molecule substantially without observable photosensitization        reactions and substantially non-radiatively.

According to some embodiments, a photoactive molecule may selected froma pigment, a porphyrin, dibenzyolmethane, p-aminobenzoic acid,anthranilate, salicylate, cinnamic acid, dihydroxycinnamic acid,camphor, trihydroxycinnamic acid, dibenzalacetone naptholsulfonate,benzalacetophenone naphtholsulfonate, dihydroxy-naphthoic acid,o-hydroxydiphenyldisulfonate, p-hydroxdydiphenyldisulfonate, coumarin,respective salts thereof, respective derivatives thereof, andcombinations thereof. A photoactive molecule may selected, in someembodiments, from coumarin and derivatives thereof; diazole derivatives;quinine derivatives and salts thereof; quinoline derivatives;hydroxyl-substituted benzophenone derivatives; naphthalate derivatives;methoxy-substituted benzophenone derivatives; uric acid derivatives;vilouric acid derivatives; tannic acid and derivatives thereof;hydroquinone; benzophenone derivatives; 1,3,5-triazine derivatives;phenyldibenzimidazole tetrasulfonate and salts and derivatives thereof;terephthalyidene dicamphor sulfonic acid and salts and derivativesthereof; methylene bis-benzotriazolyl tetramethylbutylphenol and saltsand derivatives thereof; bis-ethylhexyloxyphenol methoxyphenyl triazineand salts, diethylamino hydroxyl benzoyl and derivatives thereof; andcombinations thereof.

A composition comprising a conjugated fused polycyclic moleculeaccording to Formula I, II, and/or III may be formulated as a paint, acoating, a cosmetic, a sunscreen, a pharmaceutical preparation, abituminous preparation, an ink, a toner, a photographic emulsion, aglass, or a fabric. For example, a paint may comprise a donor moleculeand a sufficient quantity of acceptor molecules to resolve excitedstates that may arise in the donor molecules.

The present disclosure relates, in some embodiments, to methods forresolving at least one excited energy state of a photoactive molecule.For example, a method may comprise positioning a donor molecule (e.g., aphotoactive molecule and/or a photosensitizer molecule) in electricalcommunication with a conjugated fused polycyclic molecule prior to,during, or following excitation of the photoactive molecule to the atleast one excited energy state. A conjugated fused polycyclic moleculemay have a structure according to Formula I, II, or III. In someembodiments, an exicted state of a donor molecule may be resolvedsubstantially without observable photochemical reaction and/orsubstantially without observable photosensitization reactions. Anexicted state of a donor molecule may be resolved substantiallynon-radiatively, according to some embodiments. A method may comprise,in some embodiments, resolving an excited state of a donor moleculesubstantially non-radiatively, substantially without observablephotochemical reaction, and/or substantially without observablephotosensitization reactions.

The present disclosure relates, in some embodiments, to methods forresolving (e.g., quenching) excited state energy from an excited donor(e.g., a porphyrin), for example, a donor that has been excited byabsorption of light (e.g., light having a wavelength in the wavelengthrange of about 290 to about 800 nm). For example, a method may comprisereacting a donor molecule having a porphyrin moiety according to FormulaIV:

with a conjugated, fused polycyclic molecule having a structureaccording to Formula I, II, III, V, or a salt thereof. According to someembodiments, a conjugated, fused polycyclic molecule may have astructure according to Formula V:

wherein

-   -   m and n each independently may be 0, 1, 2, 3, or 4,    -   s independently may be 0 or 1,    -   A₅ independently may be O, S, C═O, C═S,

-   -   B₁, B₂, D₇, and D₈ are each independently F, Cl, Br, I, CF₃,        CCl₃, N(R₄₆)₃ ⁺, NO₂, CN, C(═O)R₄₇, C(═O)OR₄₈, SO₂R₄₉, aryl, and        —C═CHR₅₀,    -   R₄₅, R₄₇, and R₄₈ each independently may be H, alkyl, alkenyl,        alkynyl, cycloalkyl, cycloalkenyl, aryl, or amino,    -   R₄₆ each independently may be H or C₁-C₆ alkyl,    -   R₄₉ each independently may be H, O⁻, OH, NH₂, or Cl, and    -   R₅₀ each independently may be alkyl, alkenyl, alkynyl,        cycloalkyl, cycloalkenyl, or aryl.        An excited donor molecule may resolve to a lower energy state        (e.g., its ground state) upon transferring its excited electron        to a conjugated fused polycyclic molecule. In some embodiments,        an excited donor molecule and/or a conjugated fused polycyclic        molecule may be contained in a paint, a coating, a cosmetic, a        sunscreen, a pharmaceutical preparation, a bituminous        preparation, an ink, a toner, a photographic emulsion, a glass,        and/or a fabric. A donor molecule (e.g., a porphyrin) may be        contained in a mammalian cell. In some embodiments, one or more        functional groups of Formula V may be as defined for Formulas I,        II, or III including one or more exclusions. A molecule        according to Formula V may have, in some embodiments, a        molecular weight as set forth for Formulas I, II, or III.        According to some embodiments, R₄₅ may not include cycloalkenyl.

According to some embodiments, the present disclosure relates to methodsfor suppressing (e.g., arresting) the formation of one or more ofsinglet oxygen and a reactive oxygen species (e.g., superoxide anion,peroxide, hydroxyl radical, hydroxyl ion) by an excited donor molecule(e.g., an excited pigment). A donor molecule may become an excited donormolecule upon absorption of light (e.g., light having a wavelength inthe wavelength range of about 290 to about 800 nm). A method maycomprise quenching the excited donor molecule with a conjugated, fusedpolycyclic molecule having a structure according to Formula I, II, III,V, or a salt thereof.

The present disclosure relates, in some embodiments, to methods forprotecting skin from oxidative stress (e.g., caused by generation offree radical oxygen) comprising coating skin with a porphyrin excitedstate quencher capable of accepting or donating an electron from or to aporphyrin compound in the excited state and returning the excitedporphyrin compound to its ground state. A porphyrin excited statequencher may comprise, in some embodiments, a conjugated, fusedpolycyclic molecule having a structure according to Formula I, II, III,V, or a salt thereof.

The present disclosure relates, according to some embodiments, tomethods for protecting healthy cells adjacent to cancerous orpre-cancerous cells (e.g., cancerous or pre-cancerous cells undergoingphotodynamic therapy) comprising contacting (e.g., applying) acomposition comprising a porphyrin excited state quencher compound tothe adjacent healthy cells in sufficient quantity to suppress (e.g.,arrest) the formation of one or more of singlet oxygen and a reactiveoxygen species in the adjacent healthy cells. A porphyrin excited statequencher may comprise, in some embodiments, a conjugated, fusedpolycyclic molecule having a structure according to Formula I, II, III,V, or a salt thereof.

Any desired amount of acceptor (e.g., conjugated, fused polycyclicmolecule) may be used in a method of the disclosure. In someembodiments, the amount used may be related to (e.g., a function of,proportional to) the likely and/or expected exposure (e.g., duration,intensity, and/or wavelength) of a donor molecule (e.g., photoactivemolecule and/or photosensitiser molecule) to potentially excitingradiation. The amount of acceptor used may be related, in someembodiments, to (e.g., a function of, proportional to) the likely and/orexpected abundance of donor molecules (e.g., photoactive molecule and/orphotosensitiser molecule) in a composition, object, or cell to beexposed to potentially exciting radiation.

Examples of acceptor molecules that may be be included in a compositionand/or employed in one or more methods or the disclosure include one ormore conjugated, fused polycyclic molecules according to FormulaI(a)-I(j) and II(a)-II(bl) and any subset thereof. For example, a methodfor resolving at least one excited energy state of a donor molecule maycomprise positioning a donor molecule in electrical communication with aconjugated, fused polycyclic molecule selected from Formula I(a)-I(j)and II(a)-II(bl) and any subset thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

The file of this patent contains at least one drawing executed in color.Copies of this patent with color drawing(s) will be provided by thePatent and Trademark Office upon request and payment of the necessaryfee.

Some embodiments of the disclosure may be understood by referring, inpart, to the present disclosure and the accompanying drawings, wherein:

FIG. 1A illustrates an absorption spectra of an acceptor compoundaccording to a specific example embodiment of the disclosure, FormulaI(a)(1) in acetonitrile;

FIG. 1B illustrates an absorption spectra of an acceptor compoundaccording to a specific example embodiment of the disclosure, alkoxycrylene in acetonitrile;

FIG. 1C illustrates an absorption spectra of an acceptor compoundaccording to a specific example embodiment of the disclosure, FormulaII(d)(1) in acetonitrile;

FIG. 1D illustrates an absorption spectra of an acceptor compoundaccording to a specific example embodiment of the disclosure, FormulaII(a)(1) in acetonitrile;

FIG. 1E illustrates an absorption spectra of an acceptor compoundaccording to a specific example embodiment of the disclosure, FormulaII(e)(1) in acetonitrile;

FIG. 1F illustrates an absorption spectra of an acceptor compoundaccording to a specific example embodiment of the disclosure, FormulasII(b)(1) and II(c)(1) in acetonitrile;

FIG. 2A illustrates an absorption spectrum of protoporphyrin IX inacetonitrile. λex=510 nm, according to a specific example embodiment ofthe disclosure;

FIG. 2B illustrates a fluorescence spectrum of protoporphyrin IX inacetonitrile. λex=510 nm, according to a specific example embodiment ofthe disclosure;

FIG. 3A illustrates fluorescence decay traces monitored at 690 nm usingtime correlated single photon counting of the compound of FormulaI(a)(1) in acetonitrile solutions in the absence and presence ofdifferent amounts of stabilizers, according to a specific exampleembodiment of the disclosure;

FIG. 3B illustrates fluorescence decay traces monitored at 690 nm usingtime correlated single photon counting of alkoxy crylene in acetonitrilesolutions in the absence and presence of different amounts ofstabilizers, according to a specific example embodiment of thedisclosure;

FIG. 4A is a graph showing inverse fluorescence lifetime vs. acceptorconcentration used for determining k_(q), the bimolecular rate constantfor quenching of protoporphyrin IX fluorescence by the compounds ofFormula I(a)(1) and alkoxy crylene, according to a specific exampleembodiment of the disclosure, using the experimental data shown in FIG.3;

FIG. 4B is a graph showing inverse fluorescence lifetime vs. acceptorconcentration used for determining k_(q), the bimolecular rate constantfor quenching of protoporphyrin IX fluorescence by the compounds ofFormula II(a)(1), Formula II(d)(1), Formula II(e)(1), and a mixture ofFormula II(b)(1) and II(c)(1), according to a specific exampleembodiment of the disclosure;

FIG. 4C is a graph in which the data shown in FIG. 4B for FormulaII(e)(1) is plotted separate from the other data traces;

FIG. 5A illustrates a transient absorption spectrum of an argonsaturated acetonitrile solution of protoporphyrin IX, according to aspecific example embodiment of the disclosure, recorded 0.1 to 1.5 μsafter pulsed laser excitation (355 nm, 5 ns pulse width);

FIG. 5B illustrates a transient absorption spectrum of an argonsaturated acetonitrile solution of protoporphyrin IX, according to aspecific example embodiment of the disclosure, recorded 0.1 to 1.5 μsafter pulsed laser excitation (440 nm, 5 ns pulse width);

FIG. 5C illustrates a transient absorption spectrum of an argonsaturated acetonitrile solution of protoporphyrin IX, according to aspecific example embodiment of the disclosure, recorded 0.1 to 1.5 μsafter pulsed laser excitation (400 nm, 5 ns pulse width);

FIG. 6A is a graph showing inverse triplet state lifetime (measured at440 nm by laser flash photolysis) vs. acceptor concentration used fordetermining k_(q), the bimolecular rate constant for quenching ofprotoporphyrin IX triplet states by the compounds of Formula I(a)(1) andalkoxy crylene, according to a specific example embodiment of thedisclosure;

FIG. 6B is a graph showing inverse triplet state lifetime (measured at440 nm by laser flash photolysis) vs. acceptor concentration used fordetermining k_(q), the bimolecular rate constant for quenching ofprotoporphyrin IX triplet states by the compounds of Formula II(a)(1),according to a specific example embodiment of the disclosure;

FIG. 6C is a graph showing inverse triplet state lifetime (measured at440 nm by laser flash photolysis) vs. acceptor concentration used fordetermining k_(q), the bimolecular rate constant for quenching ofprotoporphyrin IX triplet states by the compounds of a mixture ofFormula II(b)(1) and II(c)(1), according to a specific exampleembodiment of the disclosure;

FIG. 6D is a graph showing inverse triplet state lifetime (measured at440 nm by laser flash photolysis) vs. acceptor concentration used fordetermining k_(q), the bimolecular rate constant for quenching ofprotoporphyrin IX triplet states by the compounds of Formula II(e)(1),according to a specific example embodiment of the disclosure;

FIG. 7A illustrates an absorption spectrum of the compound of FormulaI(a)(1) in ethanol solution at 77K, according to a specific exampleembodiment of the disclosure;

FIG. 7B illustrates a luminescence excitation spectrum of the compoundof Formula I(a)(1) in ethanol solution at 77K, according to a specificexample embodiment of the disclosure;

FIG. 7C illustrates a luminescence emission spectrum of the compound ofFormula I(a)(1) in ethanol solution at 77K, according to a specificexample embodiment of the disclosure;

FIG. 8A illustrates a singlet oxygen phosphorescence spectrum generatedby photoexcitation (532 nm) of tetrapenylporphyrin in air saturated CCl₄solutions using steady-state lamp excitation, according to a specificexample embodiment of the disclosure;

FIG. 8B illustrates a decay trace generated by photoexcitation (532 nm)of tetrapenylporphyrin in air saturated CCl₄ solutions using pulsedlaser excitation, according to a specific example embodiment of thedisclosure;

FIG. 9A illustrates inverse phosphorescence lifetime vs. absorptionmolecule concentration used to determine singlet oxygen quenching rateconstants k_(q) for Formula I(a)(1), according to a specific exampleembodiment of the disclosure;

FIG. 9B illustrates inverse phosphorescence lifetime vs. absorptionmolecule concentration used to determine singlet oxygen quenching rateconstants k_(q) for alkoxy crylene, according to a specific exampleembodiment of the disclosure;

FIG. 10 illustrates singlet oxygen phosphorescence decay tracesgenerated by pulsed laser excitation (355 nm) of protoporphyrin IX inair saturated DMSO-d₆ solutions in the absence and presence of thecompound of Formula I(a)(1), according to a specific example embodimentof the disclosure;

FIG. 11 illustrates singlet oxygen phosphorescence decay tracesgenerated by pulsed laser excitation (355 nm) of protoporphyrin IX inair saturated DMSO-d₆ solutions in the absence and presence of thealkoxy crylene compound at different concentrations, according to aspecific example embodiment of the disclosure;

FIG. 12A illustrates singlet oxygen phosphorescence spectra generated byphotoexcitation of Formula I(a)(1) and alkoxy crylene at 355 nm inbenzophenone in air saturated CCl₄ solution;

FIG. 12B illustrates and enlargement of the lower portion of FIG. 12A;

FIG. 13 illustrates an absorption spectrum and a singlet oxygenphosphorescence excitation spectrum (monitored at 1270 nm) of alkoxycrylene in air saturated CCl₄ solutions, according to a specific exampleembodiment of the disclosure;

FIG. 14A illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX (25 μM) in air saturated DMSO-d₆ solutions in theabsence and presence of the compound of Formula I(a)(1), according to aspecific example embodiment of the disclosure, monitored at 1270 nmgenerated by pulsed laser excitation at 355 nm;

FIG. 14B illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX (25 μM) in air saturated DMSO-d₆ solutions in theabsence and presence of the compound of Formula I(a)(1), according to aspecific example embodiment of the disclosure, monitored at 1270 nmgenerated by pulsed laser excitation at 532 nm;

FIG. 14C illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX (25 μM) in air saturated DMSO-d₆ solutions in theabsence and presence of an alkoxy crylene compound, according to aspecific example embodiment of the disclosure, monitored at 1270 nmgenerated by pulsed laser excitation at 355 nm;

FIG. 14D illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX (25 μM) in air saturated DMSO-d₆ solutions in theabsence and presence of an alkoxy crylene compound, according to aspecific example embodiment of the disclosure, monitored at 1270 nmgenerated by pulsed laser excitation at 532 nm;

FIG. 15A illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX dimethyl ester (25 μM) in air saturated CDCl₃solutions in the absence and presence of the compound of FormulaI(a)(1), according to a specific example embodiment of the disclosure,monitored at 1270 nm generated by pulsed laser excitation at 355 nm;

FIG. 15B illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX dimethyl ester (25 μM) in air saturated CDCl₃solutions in the absence and presence of the compound of FormulaI(a)(1), according to a specific example embodiment of the disclosure,monitored at 1270 nm generated by pulsed laser excitation at 532 nm;

FIG. 15C illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX dimethyl ester (25 μM) in air saturated CDCl₃solutions in the absence and presence of an alkoxy crylene compound,according to a specific example embodiment of the disclosure, monitoredat 1270 nm generated by pulsed laser excitation at 355 nm;

FIG. 15D illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX dimethyl ester (25 μM) in air saturated CDCl₃solutions in the absence and presence of an alkoxy crylene compound,according to a specific example embodiment of the disclosure, monitoredat 1270 nm generated by pulsed laser excitation at 532 nm;

FIG. 15E illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX dimethyl ester (25 μM) in air saturated CDCl₃solutions in the absence and presence of Formula II(a)(1), according toa specific example embodiment of the disclosure;

FIG. 15F illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX dimethyl ester (25 μM) in air saturated CDCl₃solutions in the absence and presence of Formula II(b)(1) and II(c)(1),according to a specific example embodiment of the disclosure;

FIG. 15G illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX dimethyl ester (25 μM) in air saturated CDCl₃solutions in the absence and presence of Formula II(d)(1), according toa specific example embodiment of the disclosure;

FIG. 15H illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX dimethyl ester (25 μM) in air saturated CDCl₃solutions in the absence and presence of Formula II(e)(1), according toa specific example embodiment of the disclosure;

FIG. 15I illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX dimethyl ester (25 μM) in air saturated CDCl₃solutions in the absence and presence of Formula II(a)(1), according toa specific example embodiment of the disclosure;

FIG. 15J illustrates singlet oxygen phosphorescence decay traces ofprotoporphyrin IX dimethyl ester (25 μM) in air saturated CDCl₃solutions in the absence and presence of alkoxy crylene, according to aspecific example embodiment of the disclosure;

FIG. 16A illustrates a Stern-Volmer plot of singlet oxygenphosphorescence data from decay traces of protoporphyrin IX (25 μM) inair saturated DMSO-d₆ solutions in the absence and presence of thecompound of Formula I (a)(1) and alkoxy crylene, according to a specificexample embodiment of the disclosure, monitored at 1270 nm generated bypulsed laser excitation at 355 nm;

FIG. 16B illustrates a Stern-Volmer plot of singlet oxygenphosphorescence data from decay traces of protoporphyrin IX (25 μM) inair saturated DMSO-d₆ solutions in the absence and presence of thecompound of Formula II(a)(1), according to a specific example embodimentof the disclosure, monitored at 1270 nm generated by pulsed laserexcitation at 532 nm;

FIG. 16C illustrates a Stern-Volmer plot of singlet oxygenphosphorescence data from decay traces of protoporphyrin IX (25 μM) inair saturated DMSO-d₆ solutions in the absence and presence of thecompound of Formula I(a)(1), II(b)(1), II(d)(1), II(e)(1), and alkoxycrylene, according to a specific example embodiment of the disclosure,monitored at 1270 nm generated by pulsed laser excitation at 355 nm;

FIG. 17 illustrates a scheme of quenching mechanisms of protoporphyrinIX excited states, according to a specific example embodiment of thedisclosure;

FIG. 18 illustrates the redox potential of protoporphyrin IX (FIG. 18A),Formula I(a)(1) (FIG. 18B), Formula I(a)(1) (FIG. 18C), Formula IIbi(FIG. 18D), Formula IIfi (FIG. 18E), and Formula IIci (FIG. 18F),according to a specific example embodiment of the disclosure;

FIG. 19 illustrates a comparison of the ability of a conjugated fusedpolycyclic compound, according to a specific example embodiment of thedisclosure, and ethylhexyl methoxycrylene to photostabilize solutionscomprising Avobenzone;

FIG. 20 illustrates a comparison of the ability of a conjugated fusedpolycyclic compound, according to a specific example embodiment of thedisclosure, and ethylhexyl methoxycrylene to photostabilize solutionscomprising Avobenzone and octylmethoxy cinnamate;

FIG. 21 illustrates a reduction in visible light-induced free radicalsin pig skin mediated by a conjugated fused tricycle compound accordingto a specific example embodiment of the disclosure, as assessed byelectron spin resonance;

FIG. 22 illustrates a reduction in visible light-induced reactive oxygenspecies (ROS) in human cells mediated by a conjugated fused tricyclecompound according to a specific example embodiment of the disclosure,as shown by fluorescence imaging of untreated cells (FIG. 22A), cellsirradiated in the absence of a polycyclic molecule (FIG. 22B), and cellsirradiated in the presence of a polycyclic molecule (FIG. 22C), andquantitative fluorescence assessment (FIG. 22D);

FIG. 23 illustrates the results of dosage response analyses of culturedhuman cells after exposure to visible light in the absence or presenceof a conjugated fused tricycle compound according to a specific exampleembodiment of the disclosure;

FIG. 24 illustrates the effect of incubation time on suppression of ROSaccumulation in cultured human cells after exposure to visible light inthe absence or presence of a conjugated fused tricycle compoundaccording to a specific example embodiment of the disclosure;

FIG. 25 illustrates the effect of various conjugated fused tricyclecompounds on suppression of ROS accumulation in cultured human cellsafter exposure to visible light, according to specific exampleembodiments of the disclosure;

FIG. 26 illustrates survival of cultured human cells after exposure tovisible light in the absence or presence of a conjugated fused tricyclecompound according to a specific example embodiment of the disclosure;and

FIG. 27 illustrates survival of non-irradiated cultured human cellsincubated with a conjugated fused tricycle compound according to aspecific example embodiment of the disclosure.

DETAILED DESCRIPTION

The present disclosure relates, in some embodiments, to molecules,including conjugated fused polycyclic molecules, that may receiveexcited state energy from other molecules (e.g., light-absorbingmolecules) or directly from the irradiation sources. According to someembodiments, the present disclosure relates to molecules, includingfused polycyclic molecules (e.g., conjugated fused polycyclicmolecules), that may quench, dissipate, and/or otherwise resolve excitedstate energy, normally by way of releasing it as heat. (e.g., as heat).

A light-absorbing molecule (e.g., chromophore) may absorb visible light(e.g., at about 400 to about 800 nm) and/or UV light (e.g., at about 290to about 400 nm), which causes the excitation of an electron in themolecule from an initially occupied, lower energy orbital to a higherenergy, previously unoccupied orbital. The energy of the absorbed photonis used to energize an electron and cause it to enter a higher energyorbital. Two excited electronic states derive from the electronicorbital configuration produced by visible and/or UV light absorption. Inone state, the electron spins are paired (antiparallel) and in the otherstate the electron spins are unpaired (parallel). The state with pairedspins has no resultant spin magnetic moment, but the state with unpairedspins possesses a net spin magnetic moment. A state with paired spinsremains a single state in the presence of a magnetic field, and istermed a singlet state. A state with unpaired spins interacts with amagnetic field and splits into three quantized states, and is termed atriplet state.

When light-absorbing molecules are in an electronically excited state asa result of photon absorption, they can transfer excited state energy toother species to generate reactive products. For example, excitedlight-absorbing molecules can transfer excited state energy to oxygen,which may result in the generation of reactive oxygen species (e.g.,singlet oxygen, free radical oxygen, superoxide anion, peroxide,hydroxyl radical, and hydroxyl ion). Formation of these species oftenresults in unwanted effects including, for example, physical andchemical damage to nearby molecules. This damage can lead to loss ofdesired coloration of colored compositions, reduction of structuralintegrity (e.g., polymeric compounds), and/or irreversible changes tobioactive molecules in living cells.

Colorants may be substances that impact color by reflecting and/ortransmitting light as a result of wavelength-selected absorption.Colorants may combined with other molecules and/or included incompositions (e.g., paints, coatings, inks, plastics, fabrics,cosmetics, food) to modify the appearance of the mixture. Organic dyesmay be colorants that are either liquids themselves, or they aredissolved in a liquid to produce a solution. Organic pigments may becolorants that may be insoluble in one or more particular vehicles, andresult in suspensions. Colorants may include organic dyes and organicpigments. A colorant may be or may comprise a chromophore capable ofentering one or more excited states when exposed to UV and visiblelight, such as sunlight. An excited state may lead to undesirablephotobleaching of colorants.

Polymeric materials may be included in, for example, coatings, moldings,paints, inks, and the like. Reactive oxygen species (“ROS”) mayphotooxidize polymers. For example, hydroperoxide groups, aldehydes, andketones may form on the polymer backbone upon exposure to ROS.Photooxidation may result in, for example, chain scission (e.g., reducedmolecular weight), crosslinking (e.g., increased molecular weight),secondary oxidative reactions, and/or combinations thereof. Aphotooxidized polymer material may be altered, appearing weathered,discolored, and/or coarse relative to an unoxidized material.Consequences (e.g., unwanted consequences) of such polymer degradationmay include altered strength (e.g., tensile strength, impact strength),elasticity, resilience, rigidity, ductility, and/or combinationsthereof. It may be desirable, therefore, to return electronicallyexcited chromophores to the ground state before they can transferexcited state energy to a oxygen molecules, according to someembodiments.

The present disclosure relates, in some embodiments, to molecules thatmay receive excited state energy from other molecules (e.g.,light-absorbing molecules). According to some embodiments, the presentdisclosure also relates to molecules that may quench, dissipate, and/orotherwise resolve excited state energy. A molecule that donates excitedstate energy may be referred to as a donor molecule and/or a moleculethat receives excited state energy may be referred to as a receiver oracceptor molecule in some embodiments. An acceptor molecule maycomprise, for example, a conjugated fused polycyclic molecule. In someembodiments, a donor molecule may be a photoactive—it may absorbincident radiation (e.g., UV radiation). For example, a molecule exposedto light may absorb one or more photons. Absorbed energy (e.g., photons)may raise a low energy state electron (e.g., ground state electron) toan excited energy state (e.g., singlet or triplet). Formation and/orresolution of the excited energy state may lead to unwanted effectsincluding, for example, formation of radicals and/or chemical breakdownof polymers, dyes, and/or pigments.

Various strategies may be adopted for mitigating the adverse effects ofpotentially exciting energy sources (e.g., light). For example, theobject may be isolated from potentially exciting energy sources.Isolation may include a complete photo, electro, and/or thermaldisconnect between the potential source(s) and the object to beprotected. Another strategy may include filtering the potentialsource(s) such that the object and potential source are in limitedphoto, electro, and/or thermal communication. For example, light may befiltered (e.g., using a sunscreen) such that less or no radiation canreach the object to produce adverse effects in the object. In yetanother approach, adverse effects from potentially exciting energysources may also be mitigated by limiting or preventing free radicaldamage. For example, anti-oxidants may be added to react with the freeradicals formed before the radicals have an opportunity to interact withand damage the object to be protected.

These strategies may not always produce desired results. Accordingly, itmay be desirable to move upstream in the excitation process. Forexample, preventing radical formation may have advantages over applyingantioxidants afterwards. Isolation and/or filtering techniques may beemployed to prevent formation of the excited energy state. However,these approaches may not be satisfactory either, for example, whereexposure of the object to the potentially exciting energy source isdesirable, necessary and/or inevitable.

According to some embodiments, the present disclosure relates tomolecules, compositions, systems, and methods for promptly resolvingexcited energy states after formation. Excited state resolution mayoccur through a pathway or pathways that mitigate or prevent unwantedand/or harmful effects (e.g., radical formation, sensitization ofsurrounding molecules, producing unwanted photoproducts).

According to some embodiments, compositions, systems, and methods of thepresent disclosure may be operable without regard to the source of theexcitation energy. For example, excited energy states may be resolvedwhere the excited state arose from another excited species by way ofsensitization and/or direct electromagnetic radiation of any wavelengthsufficient to eject an electron from its ground state to an excitedstate. Examples of electromagnetic radiation include visible light,ultra violet radiation, and X-rays. Thus, molecules and compositionsaccording to some embodiments of the disclosure may provide a broadspectrum of protection. For example, protection may be provided in a UVrange through filtering and/or quenching and/or in a visible range byquenching.

In some embodiments, the present disclosure relates to conjugated fusedpolycyclic molecules. For example, a conjugated fused polycyclicmolecule may comprise a conjugated fused tricyclic molecule. Aconjugated fused polycyclic molecule may include and/or may exclude anydesired atom or functional group, according to some embodiments. Forexample, a conjugated fused polycyclic molecule may exclude halogens,silicon and/or selenium. Each ring of a conjugated fused polycyclicmolecule may have, in some embodiments, about 3 to about 8 members. Forexample, a polycyclic molecule may include a fused tricyclic moiety inwhich the rings are designated X, Y, and Z. Rings X and Y may have 6members each, interposed by ring Z having 5 or 6 members. Rings X, Y,and Z may be co-planar, for example, to increase or maximize electrondelocalization and/or regulating reduction potential.

A conjugated fused polycyclic compound may have, according to someembodiments, a structure according to Formula I or a salt thereof:

wherein

-   -   R₁ may be independently nitrile, C(O)R₃, C(O)N(R₄)R₅, C(O)—S—R₆,        or fused aryl,    -   R₂ may be independently nitrile, C(O)R₇, C(O)N(R₈)R₉,        C(O)—S—R₁₀, or fused aryl,    -   R₃, R₄, R₅, R₆, R₇, R₈, R₉, and R₁₀ may be independently H,        aryl, substituted aryl, fused aryl, alkyl, substituted alkyl, or        branched alkyl,    -   D₁ may be independently H, hydroxyl, or R₁₁,    -   D₂ may be independently H, hydroxyl, or R₁₂,    -   R₁₁ and R₁₂ may be independently H, alkyl, heteroalkyl, alkoxyl,        heteroalkoxyl, aryl, heteroaryl, or fused aryl,        provided that    -   R₁ and R₂ are not both nitrile,    -   R₁ and R₂ are not fused to each other,    -   R₁₁ and R₁₂ do not comprise azo,    -   the fused tricyclic moiety defined by rings X, Y, and Z is the        only tricyclic moiety in the molecule, and    -   D₁ and D₂ are not fused to each other.

In some embodiments, R₁ may further comprise C(O)OR₃ or aryl and/or R₂may further comprise C(O)OR₇ or aryl. R₁ and/or R₂ may comprise one ormore electron-withdrawing groups. Substitutions (e.g., on rings X and Y)may be chosen for ready non-radioactive decay (e.g., para substitution),in some embodiments.

According to some embodiments, a conjugated fused polycyclic moleculemay have a molecular weight of less than about 2,000, less than about1,800, less than about 1,600, less than about 1,400, less than about1,200, less than about 1,000, less than about 900, less than about 800,less than about 750, less than about 700, less than about 650, less thanabout 600, less than about 550, and/or less than about 500. For example,a conjugated fused polycyclic molecule may have a molecular weight ofabout 240 to about 750. Ring X and D₁ together may have a molecularweight of up to about 500 (e.g., up to about 400, up to about 300, up toabout 250, about 75 to about 200, about 75 to about 300, andcombinations thereof). Ring Y and D₂ together may have a molecularweight of up to about 500 (e.g., up to about 400, up to about 300, up toabout 250, about 75 to about 200, about 75 to about 300, andcombinations thereof), according to some embodiments. R₁ and/or R₂ eachindependently may have a molecular weight of up to about 500 (e.g., upto about 400, up to about 300, up to about 250, about 40 to about 200,about 40 to about 300, and combinations thereof).

Examples of Formula I may include Formulas I(a)-I(i):

wherein each R may be independently selected from R₁, R₂, R₃, R₄, R₅,R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂, and/or combinations thereof. In someembodiments, substituents (e.g., R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉,R₁₀, R₁₁, R₁₂, D₁, D₂) may be the same or different. According to someembodiments, substituents may be independently selected. In someembodiments, each R may be C₁-C₃₀ alkyl, C₁-C₂₀ alkyl, or C₁-C₁₀ alkyl.For example, R may include, but is not limited to, methyl, ethyl,propyl, isopropyl, or 2-ethylhexyl.

According to some embodiments, an aryl group may comprise a carbocyclicaromatic ring system having a single ring, two fused rings, or threefused rings. An aryl group may be selected from phenyl, naphthyl,tetrahydronaphthyl, phenanthrenyl, biphenylenyl, indanyl, indenyl,anthracenyl, and fluorenyl.

An alkyl group may comprise, in some embodiments, a straight- and/orbranched-chain saturated hydrocarbon having from about 1 to about 30(C1-C30) or more carbon atoms. Examples of alkyl groups may includemethyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl(2-methylpropyl),t-butyl(1,1-dimethylethyl), and 3,3-dimethylpentane. An alkoxyl groupmay comprise —O-alkyl, in some embodiments.

A substituted alkyl group may comprise, in some embodiments, an alkylhaving one or more substituents. Substituents may include, for example,heteroalkyl, ester, carboxy, cyano, amino, amido, sulfur, and/or halo.In some embodiments, a substituted alkyl group may be mono-, di-, ortri-substituted at each of one, two, or three carbon atoms. Substituentsmay be present on a single carbon or distributed among more than onecarbon.

A nitrile group (also called a cyano group) may comprise a —C≡N (also“—CN”), in some embodiments.

Formula I, in some embodiments, excludes 9-(dicyanomethylene)fluorine(e.g., because R₁ and R₂ cannot both be nitrile if D₁ and D₂ arehydrogen).

According to some embodiments, R₁ and R₂ may be the same or different.For example, R₁ and R₂ may be selected to be different from each other.R₁ and R₂ may be selected, according to some embodiments, such that thetwo are distinct from each other (e.g., not fused to each other forminga 5 or 6 member ring). In some embodiments, R₁ cannot be nitrile if R₇is a branched alkyl. R₃ cannot be a branched alkyl if R₂ is nitrile,according to some embodiments. R₃ and R₇ cannot be methyl or ethyl,according to some embodiments. For example, R₃ and R₇ may be selected toexclude methyl and ethyl where D₁ and/or D₂ comprise an ethylene groupand/or a ketone. In some embodiments, R₁ may exclude C(O)OR₃ and/orexclude aryl. R₂ may likewise exclude C(O)OR₇ and/or exclude aryl.

D₁ and/or D₂, according to some embodiments, may be selected to excludean azo group (e.g., —N═N—), an imine group (e.g., —N═C—), a nitro group(e.g., —NO₂), an ethylene group (e.g., non-aryl —C═C—), an ester group(e.g., —C(O)—O—), a sulfone group, a ketone group, a nitrile group, acarboxyl group (e.g., —COOH), a ketone, a thio ether group (e.g., —S—),and/or combinations thereof. According to some embodiments, D₁ and/or D₂may be selected to exclude a group that comprises an azo group, an iminegroup, a nitro group, an ethylene group, an ester group, a sulfonegroup, a ketone group, a nitrile group, a carboxyl group, a ketone, athio ether group, and/or combinations thereof. D₁ and/or D₂, accordingto some embodiments, may be selected to be the same or different. D₁ mayinclude a ring that is fused to ring X according to some embodiments. D₂may include, in some embodiments, a ring that is fused to ring Y. Insome embodiments, D₁ and D₂ cannot both be —H. D₁ and D₂, according tosome embodiments, are distinct from each other (e.g., not fused to eachother forming a ring). For example, D₁ and D₂ may be distinct if R₁ andR₂ are both nitrile. D₁ and R₁ may be distinct from each other (e.g.,not fused to each other forming a ring). D₂ and R₂ may be distinct fromeach other (e.g., not fused to each other forming a ring). In someembodiments, D₁ may exclude alkenyl, D₂ may exclude alkenyl, or D₁ andD₂ may both exclude alkenyl.

D₁ and/or D₂ may be joined, according to some embodiments, to rings Xand/or Z, respectively, by any desired bond. In some embodiments, D₁and/or D₂ may be joined to rings X and/or Z, respectively, by any bondother than a carbonyl (e.g., D-C(O)—X) and/or any bond other than anester (e.g., D-C(O)—O—X, X—C(O)—O-D). According to some embodiments,Ring X may comprise no substituents other than D₁ and/or ring Z maycomprise no substituents other than D₂.

According to some embodiments, if R₁ and R₂ are both nitrile, D₁ and/orD₂ may be selected to exclude an azo group, an imine group, a nitrogroup, an ethylene group, an ester group (e.g., a butyl ester group), asulfone group, a nitrile group, a carboxyl group, a thio ether group,and/or combinations thereof. If R₁ is nitrile and R₂ is a substitutedaryl (or vice versa), D₁ and/or D₂ may be selected to exclude a nitrogroup, in some embodiments.

A conjugated fused polycyclic compound may have, according to someembodiments, a structure according to Formula II or a salt thereof:

wherein

-   -   A₁ may be independently carbonyl, C═C(R₁₃)R₁₄, O, S, S═O,        S(O)═O, C═S,    -   R₁₃ may be independently nitrile, C(O)OR₁₅, C(O)R₁₆,        C(O)N(R₁₇)R₁₈, C(O)—S—R₁₉, aryl, substituted or fused aryl,    -   R₁₄ may be independently nitrile, C(O)OR₂₀, C(O)R₂₁,        C(O)N(R₂₂)R₂₃, C(O)—S—R₂₄, aryl, substituted or fused aryl,    -   R₁₅, R₁₆, R₁₇, R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, and R₂₄, may be        independently aryl, substituted aryl, fused aryl, alkyl,        substituted alkyl, or branched alkyl,    -   A₂ may be independently carbonyl, C═C(R₁₃)R₁₄, O, S, S═O,        S(O)═O, C═S,    -   D₃ may be independently H, hydroxyl, or R₂₅,    -   D₄ may be independently H, hydroxyl, or R₂₆,    -   R₂₅ may be independently alkyl, heteroalkyl, alkoxyl,        heteroalkoxyl, aryl, heteroaryl, or fused aryl,    -   R₂₆ may be independently alkyl, heteroalkyl, alkoxyl,        heteroalkoxyl, aryl, heteroaryl, or fused aryl,        provided that    -   at least one of A₁ and A₂ is C═C(R₁₃)R₁₄,    -   if neither A₁ nor A₂ is S, for each C═C(R₁₃)R₁₄, no more than        one of R₁₃ and R₁₄ is nitrile (e.g., if both A₁ and A₂ are        C═C(R₁₃)R₁₄, no more than one of R₁₃ and R₁₄ of the A₁ group may        be nitrile and no more than one of R₁₃ and R₁₄ of the A₂ group        may be nitrile), and    -   if either A₁ nor A₂ is O, for each C═C(R₁₃)R₁₄, no more than one        of R₁₃ and R₁₄ is C(O)OR_(15/20) (i.e., if R₁₃ is C(O)OR₁₅, R₁₄        cannot be C(O)OR₂₀ and vice versa).

According to some embodiments, R₁ and/or R₂ may comprise one or moreelectron-withdrawing groups. Substitutions (e.g., on rings X and Y) maybe chosen for ready non-radioactive decay (e.g., para substitution), insome embodiments.

According to some embodiments, a conjugated fused polycyclic moleculemay have a molecular weight of less than about 2,000, less than about1,800, less than about 1,600, less than about 1,400, less than about1,200, less than about 1,000, less than about 900, less than about 800,less than about 750, less than about 700, less than about 650, less thanabout 600, less than about 550, and/or less than about 500. For example,a conjugated fused polycyclic molecule may have a molecular weight ofabout 240 to about 750. Ring X and D₃ together may have a molecularweight of up to about 500 (e.g., up to about 400, up to about 300, up toabout 250, about 75 to about 200, about 75 to about 300, andcombinations thereof). Ring Y and D₄ together may have a molecularweight of up to about 500 (e.g., up to about 400, up to about 300, up toabout 250, about 75 to about 200, about 75 to about 300, andcombinations thereof), according to some embodiments. A₁, A₂, R₁₀ and/orR₁₁ each independently may have a molecular weight of up to about 500(e.g., up to about 400, up to about 300, up to about 250, about 40 toabout 200, about 40 to about 300, and combinations thereof).

Examples of Formula II may include Formulas II(a)-II(bj):

wherein each R may be independently selected from R₁₃, R₁₄, R₁₅, R₁₆,R₁₇, R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, R₂₄, R₂₅, R₂₆, and/or combinationsthereof. In some embodiments, substituents (e.g., A₁, A₂, R₁₃, R₁₄, R₁₅,R₁₆, R₁₇, R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, R₂₄, R₂₅, R₂₆, D₃, D₄) may bethe same or different. According to some embodiments, substituents maybe independently selected. In some embodiments, each R may be C₁-C₃₀alkyl, C₁-C₂₀ alkyl, or C₁-C₁₀ alkyl. For example, R may include, but isnot limited to, methyl, ethyl, propyl, isopropyl, or 2-ethylhexyl.

Formula II, in some embodiments, excludes:

(e.g., because R₁₃ cannot be C(O)OR₁₅ where R₁₄ is C(O)OR₂₀).

According to some embodiments, D₃ and D₄ may not comprise an azo group.For example, D₃ and D₄ may exclude azo where R₁₃ and R₁₄ are nitrile andA₁ is a carbonyl group. D₃ and D₄ may exclude azo where R₁₃ and R₁₄ arenitrile and A₂ is a carbonyl group. D₃ and D₄ may not comprise, in someembodiments, an amine (e.g., a primary amine). For example, D₃ and D₄may exclude a primary amine where R₁₃ and R₁₄ are nitrile and A₁ is acarbonyl group. D₃ and D₄ may exclude a primary amine where R₁₃ and R₁₄are nitrile and A₂ is a carbonyl group. D₃ and D₄ may not comprise animine group, according to some embodiments. For example, D₃ and D₄ mayexclude an imine group where R₁₃ and R₁₄ are nitrile.

In some embodiments, D₃ and D₄ may not comprise a nitro group. Forexample, D₃ and D₄ may not comprise a nitro group where R₁₃ and R₁₄ arenitrile and A₁ is —O—. D₃ and D₄ may not comprise a nitro group whereR₁₃ and R₁₄ are nitrile and A₂ is —O—. D₃ and D₄ may not comprise,according to some embodiments, a methylether group (e.g., a —OCH₃). Forexample, D₃ and D₄ may not comprise a methylether group where R₁₃ andR₁₄ are nitrile and A₁ is —O—. D₃ and D₄ may not comprise a methylethergroup where R₁₃ and R₁₄ are nitrile and A₂ is —O—.

D₃ and D₄ may not comprise an ethylene group (e.g., a non-aromatic,non-cyclic, carbon-carbon double bond), according to some embodiments.For example, D₃ and D₄ may exclude an ethylene group where the ethylenejoins a fused polycyclic molecule to a backbone, other identical orsimilar polycyclic moieties, or to a polymer or other macromolecule. D₃and D₄ may exclude an ethylene group where R₁₃ and R₁₄ are nitrile.

In some embodiments, R₁₅ and R₂₀ may not comprise a methyl group. Forexample, R₁₅ and R₂₀ may not comprise a methyl group where A₁ is —O—.R₁₅ and R₂₀ may not comprise a methyl group where A₂ is —O—. R₁₅ and R₂₀may not comprise, in some embodiments, an ethyl group. For example, R₁₅and R₂₀ may not comprise an ethyl group where A₁ is —O—. R₁₅ and R₂₀ maynot comprise an ethyl group where A₂ is —O—.

D₃ and/or D₄ may be joined, according to some embodiments, to rings Xand/or Z, respectively, by any desired bond. In some embodiments, D₃and/or D₄ may be joined to rings X and/or Z, respectively, by any bondother than a carbonyl (e.g., D-C(O)—X) and/or any bond other than anester (e.g., D-C(O)—O—X, X—C(O)—O-D). According to some embodiments,Ring X may comprise no substituents other than D₃ and/or ring Z maycomprise no substituents other than D₄.

In some embodiments, a molecule of Formula I or Formula II may compriseat least three fused conjugated rings and may have a total of up to 3rings, up to 4 rings, up to 5 rings, or up to 6 rings. A molecule ofFormula I or Formula II may have, according to some embodiments, up to 4rings fused to each other. In some embodiments, a molecule of Formula Ior Formula II may include a single atom that is shared by up to 3 rings.A molecule of Formula I or Formula II may include no more than one atomthat is shared by 3 rings and/or no atoms that are shared by more than 3rings, according to some embodiments. Two rings fused to each other mayshare 2 atoms (e.g., carbon atoms) and 1 bond (e.g., single bond, doublebond, conjugated pi bond) according to some embodiments.

A conjugated fused polycyclic molecule according to Formula I may haveand/or may require R₁, R₂, R₃, R₄, R₅, R₆, R₇, R₈, R₉, R₁₀, R₁₁, R₁₂,D₁, and/or D₂ to have a structure other than a polymeric structure, insome embodiments. A conjugated fused polycyclic molecule according toFormula II may have and/or may require A₁, A₂, R₁₃, R₁₄, R₁₅, R₁₆, R₁₇,R₁₈, R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, R₂₄, R₂₅, R₂₆, D₃, and/or D₄ to have astructure other than a polymeric structure, in some embodiments. Forexample, a conjugated fused polycyclic molecule may comprise only onetricyclic group (e.g., rings X, Y, and Z) per molecule. A conjugatedfused polycyclic molecule may have a monomeric and/or non-repeatingstructure, in some embodiments. A free conjugated fused polycyclicmolecule, according to some embodiments, may be soluble in a selectedsolvent and/or may not be covalently linked to a polymer.

According to some embodiments, a polymeric structure may comprise astep-growth polymer such as a polyester, a polyamides, or apolyurethane. The polymer structure can also be a chain-growth polymersuch as a polyacrylate, a polystyrene, a polyolefine and theirco-polymer.

In some embodiments, a conjugated fused polycyclic molecule may resolvean excited state according to a mechanism comprising:

wherein A is a light-absorbing donor molecule and B is a conjugatedfused polycyclic acceptor molecule.

A conjugated fused polycyclic compound may have, according to someembodiments, a structure according to Formula III or a salt thereof:

wherein

-   -   m and n each independently may be 0, 1, 2, 3, or 4,    -   r and s each may be 0 or 1,    -   A₃ and A₄ each independently may be carbonyl, C═C(R₂₇)R₂₈, O, S,        S═O, S(O)═O, or C═S,    -   R₂₇ may be nitrile, C(O)OR₂₉, C(O)R₃₀, C(O)N(R₃₁)R₃₂,        C(O)—S—R₃₃, C(O)—O—S—R₃₄, C═CHR₃₅, N(R₃₆)₃ ⁺, F, Cl, Br, I, CF₃,        CCl₃, NO₂, aryl, substituted aryl, or fused aryl,    -   R₂₈ may be nitrile, C(O)OR₃₇, C(O)R₃₈, C(O)N(R₃₉)R₄₀,        C(O)—S—R₄₁, C(O)—O—S—R₄₂, C═CHR₄₃, N(R₄₄)₃ ⁺, F, Cl, Br, I, CF₃,        CCl₃, NO₂, aryl, substituted aryl, or fused aryl,    -   R₂₉ and R₃₇ each independently may be H, alkyl, cycloalkyl,        alkenyl, cycloalkenyl, alkynyl, aryl, substituted aryl, or fused        aryl,    -   R₃₀, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, R₃₈, R₃₉, R₄₀, R₄₁, R₄₂, and R₄₃        each independently may be H, alkyl, cycloalkyl, alkenyl,        cycloalkenyl, alkynyl, or aryl, substituted aryl, or fused aryl,        alkyl, substituted alkyl, or branched alkyl,    -   R₃₆ and R₄₄ each independently may be H or C₁-C₆ alkyl, and    -   D₅ and D₆ may be independently R₂₇, R₂₈, heteroaryl, hydroxyl,        alkyl, or alkoxyl, provided that    -   r+s≧1, and    -   at least one of A₃ and A₄ is C═C(R₂₇)R₂₈.        According to some embodiments, R₁ and/or R₂ may comprise one or        more electron-withdrawing groups. Substitutions (e.g., on rings        X and Y) may be chosen for ready non-radioactive decay (e.g.,        para substitution), in some embodiments.

The present disclosure relates, in some embodiments, to a compositionsfor resolving an electronically excited state of a donor molecule.Compositions may include at least one donor molecule and at least oneacceptor molecule, according to some embodiments. Compositions may beformulated for any desired application. For example, compositions may beformulated for industrial, cosmetic, culinary, pharmaceutical, medical,and/or recreational uses. Compositions may include, in some embodiments,paints (e.g., paints for cars, boats, aircraft, buildings, signs,roadways, and any other building or structure exposed to light),coatings (e.g., clear coatings), textiles (e.g., woven or non-wovenfabrics), polymers (e.g., plastics, rubbers), bituminous materials,inks, toners, photographic emulsions, glass, make-up materials, suncarematerials, and combinations thereof.

In some embodiments, a composition comprising a donor and/or acceptormolecule may be formulated for use in or with roofing materials. Forexample, an acceptor and/or a donor may be included in an underlayment,a bituminous material, a resin (e.g., bonded to a reinforcing mat), acovering layer, and/or an adhesive.

Donor molecules may include, for example, photounstable visible lightabosorbers and UV light absorbers. Donors may be sensitizers (e.g.,photosensitizers), in some embodiments. Examples of donor molecules mayinclude, according to some embodiments, pigments, porphyrins,riboflavins, melanins, azo, xanthene, phenothiazinium, triphenylmethane, and/or dibenzoylmethane derivatives. For example, it has beenfound that conjugated fused polycyclic molecules may resolve (e.g.,quench) the singlet and/or triplet excited energy state of photounstablevisible light and photounstable UV light absorbers. Transfer of excitedstate energy from a donor molecule to an acceptor molecule may result inreturning the donor molecule to its ground state and/or reduction in thegeneration of singlet oxygen or other unwanted effects. Where acomposition is a topical for application to skin, the contacted skin maybe relieved of at least some of the oxidative stress to which it wouldhave otherwise been exposed.

Accordingly, by applying one or more of the conjugated fused tricycliccompounds, in a dermatologically or cosmetically acceptable carrier,onto mammalian skin, e.g., human skin, the skin may not suffer fromoxidative stress due to the generation of potentially cytotoxic singletoxygen. Thus, the compositions and methods described hereinadvantageously quench the excited state reached by dibenzoylmethanederivatives, porphyrins, and/or related chromophores endogenous to humanskin, thereby significantly reducing the generation of singlet oxygen incells and preventing oxidative stress.

In some embodiments, a method may comprise contacting a photolabilevisible light and/or UV absorber (e.g., excited to a singlet and/ortriplet excited state) with a with a conjugated fused polycycliccompound. As a result, the light absorber is returned to its groundstate so that it can absorb more UV radiation, thereby protecting theskin for longer durations.

Photounstable UV absorber may include, for example, dibenzoylmethanederivatives, such as butylmethoxy dibenzoylmethane (Avobenzone).Porphyrins may include, for example, protoporphyrin IX and otherendogenous chromophores. Donor and/or acceptor molecules may be includedin photoactive sunscreen, cosmetic and dermatological compositions.

According to some embodiments, the present disclosure relates tocompositions for resolving an excited state of a donor molecule. Acomposition may comprise, for example, a molecule of Formula I, II,and/or III. In some embodiments, where R₁, R₂, R₁₃, and R₁₄ are selectedfrom nitrile and C(O)OMe, R₁≠R₂, and R₁₃≠R₁₄, a compound of Formula I,II or III may be selected from:

and/or combinations thereof.

According to some embodiments, where R₁═R₂═C(O)OMe, A₁ is C═C(R₁₃)R₁₄,for which R₁₃, ═R₁₄═C(O)OMe, and A₂ is as shown in Formula II, acompound of Formula I, II or III may be selected from:

and/or combinations thereof.

A conjugated fused polycyclic compound of Formulas I, II, and/or III maybe included in a composition (e.g., a cosmetic or dermatologicalcomposition) at any desired concentration. For example, conjugated fusedpolycyclic compound may be included in a cosmetic or dermatologicalcomposition in an amount of about 0.01% by weight to about 20% byweight, from about 0.1 to about 20% by weight, or from about 0.1% toabout 10% by weight, in each case based on the total weight of thecomposition.

In some embodiments, a donor molecule may comprise a pigment (e.g., aporphyrin). A photodegradable pigment may include, according to someembodiments, exogenous pigments, such as exogenous porphyrin compounds,or endogenous pigments, such as non-hematogenous pigments, hematogenous(i.e., blood derived) pigments, or mixtures thereof. In someembodiments, an endogenous photodegradable pigment is a non-hematogenouspigment, such as, for example, melanins, flavins, pterins, and/orurocanic acid. A photodegradable non-hematogenous pigment may comprise,in some embodiments, a melanin, such as, for example, eumelanin,pheomelanin, neuromelanin, or mixtures thereof. According to someembodiments, a photodegradable non-hematogenous pigment may comprise aflavin, such as, for example, riboflavin, flavin mononucleotide, aflavoprotein, and/or flavin adenine dinucleotide. A photodegradablenon-hematogenous pigment may comprise a pterin, such as, for example,pteridine, biopterin, tetrahydrobiopterin, molybdopterin, cyanopterin,tetrahydromethanopterin, folic acid, and combinations thereof, accordingto some embodiments. A photodegradable endogenous pigment may be, insome embodiments, a hematogenous pigment, for example, hemoglobin, bilepigments, porphyrins, and mixtures thereof. In some embodiments, thephotodegradable hematogenous pigment is a bile pigment. In someembodiments, the bile pigment is bilirubin, biliverdin, or a mixturethereof.

A porphyrin may have its singlet and/or triplet excited states resolved(e.g., quenched) by a conjugated fused polycyclic molecule, according tosome embodiments. A porphyrin may comprise the moiety of Formula IV (andderivatives and tautomers thereof), as shown in Formula IVa, and FormulaIVb (protoporphyrin IX). Porphyrins are a group of organic compounds,mainly naturally occurring. One of the best-known porphyrins is heme,the pigment in red blood cells.

Heme is a cofactor of the protein hemoglobin. Porphyrins areheterocyclic macrocycles composed of four modified pyrrole subunitsinterconnected at their a carbon atoms via methine bridges (═CH—), asshown in Formula I. Porphyrins are aromatic. That is, they obey Hückel'srule for aromaticity, possessing 4n+2 π electrons (n=4 for the shortestcyclic path) delocalized over the macrocycle. Thus, porphyrinmacrocycles are highly conjugated systems and typically have veryintense absorption bands in the visible region and may be deeplycolored. The macrocycle has 26 π electrons in total. The parentporphyrin is porphine, and substituted porphines are called porphyrins.

According to some embodiments, a porphyrin without a metal-ion in itscavity is a free base. A porphyrin may comprise a chelated metal (e.g.,having a 2+ or 3+ oxidation state), in some embodiments. A chelatedmetal may include, for example, beryllium, magnesium, aluminum, calcium,strontium, barium, radium, scandium, titanium, vanadium, chromium,manganese, iron, cobalt, nickel, copper, zinc, gallium, yttrium,zirconium, niobium, molybdenum, technetium, ruthenium, rhodium,palladium, silver, cadmium, indium, tin, lead, and platinum.

Some iron-containing porphyrins are called hemes. Heme-containingproteins, or hemoproteins, are found extensively in nature. Hemoglobinand myoglobin are two O₂-binding proteins that contain iron porphyrins.Various cytochromes are also hemoproteins.

A porphyrin molecule in an electronically excited state can transfer itsexcited state energy to oxygen contained in blood and/or skin cells,thereby generating cell-damaging singlet excited state oxygen(hereinafter “singlet oxygen”), or free radical oxygen. According tosome embodiments, a system may photostabilize the excited state of theporphyrin molecule so that it does not generate cell-toxic singletoxygen, for example, by resolving the excited state of the porphyrinmolecule, returning it to the ground state before it transfers itsexcited state energy to nearby oxygen molecule.

A porphyrin may include, in some embodiments, a porphyrin moietyaccording to Formula IV:

A porphyrin may include, in some embodiments, a porphyrin moietyaccording to Formula IV(a):

wherein:each Q₁ may be independently selected from H, alkyl, alkenyl, alkynyl,hydroxyl, alkoxyl, carboxyl, carboxylic ester, amino, sulfhydryl, aryl,and heteroaryl; and,each Q₂ may independently selected from H, alkyl, alkenyl, alkynyl,hydroxyl, alkoxyl, carboxyl, carboxylic ester, amino, sulfhydryl, aryl,and heteroaryl.

In some embodiments, each Q₁ may be independently selected from thegroup consisting of H, C₁-C₆ unsubstituted alkyl, C₁-C₆ hydroxyalkyl,C₁-C₆ carboxyalkyl, C₁-C₆ esteralkyl, C₁-C₆ sulfhydrylalkyl C₁-C₆alkenyl, amino, aryl, and heteroaryl.

In some exemplary embodiments, each Q₁ may be independently selectedfrom the group consisting of H, C₁-C₄ unsubstituted alkyl, C₁-C₄hydroxyalkyl, C₁-C₄ carboxyalkyl, C₁-C₄ esteralkyl, C₁-C₆sulfhydrylalkyl, C₁-C₄ alkenyl, aryl, and heteroaryl. For example, eachQ₁ may be independently selected from the group consisting of H, methyl,ethyl, propyl, isopropyl, n-butyl, sec-butyl, iso-butyl, tert-butyl,ethenyl, 1-propenyl, 2-propenyl, 1-hydroxyethyl, 2-hydroxyethyl, phenyl,acetic acid, methyl acetate, ethyl acetate, propionic acid, methylpropanate, ethylpropanate, and

In some embodiments, each Q₂ may be independently selected from H, C₁-C₆alkyl, C₁-C₆ alkenyl, aryl, and heteroaryl. Each Q₂ may be independentlyselected from H, C₁-C₄ alkyl, C₁-C₄ alkenyl, phenyl, naphthyl, andpyridyl, in some embodiments. For example, each Q₂ may be independentlyselected from H, phenyl, hydroxyphenyl, dihydroxyphenyl,trihydroxyphenyl, methoxyphenyl, dimethoxyphenyl, trimethoxyphenyl,carboxyphenyl, trimethylanilinium, naphthyl, sulfonatophenyl, pyridyl,and N-methylpyridyl.

Examples of a porphyrins that may attain an excited state may include5-azaprotoporphyrin IX, bis-porphyrin, coproporphyrin III,deuteroporphyrin, deuteroporphyrin IX dichloride, diformyldeuteroprophyrin IX, dodecaphenylporphyrin, hematoporphyrin,hematoporphyrin IX, hematoporphyrin monomer, hematoporphyrin dimer,hematoporphyrin derivative, hematoporphyrin derivative A,hematoporphyrin IX dihydrochloride, hematoporphyrin dihydrochloride,mesoporphyrin, mesoporphyrin IX, monohydroxyethylvinyl deuteroporphyrin,5,10,15,20-tetra(o-hydroxyphenyl)porphyrin,5,10,15,20-tetra(m-hydroxyphenyl)porphyrin,5,10,15,20-tetra(p-hydroxyphenyl) porphyrin,5,10,15,20-tetrakis(3-methoxyphenyl)-porphyrin,5,10,15,20-tetrakis(3,4-dimethoxyphenyl)porphyrin,5,10,15,20-tetrakis(3,5-dimethoxyphenyl)porphyrin,5,10,15,20-tetrakis(3,4,5-trimethoxyphenyl)porphyrin,2,3,7,8,12,13,17,18-octaethyl-5,10,15,20-tetraphenylporphyrin, porphyrinc, protoporphyrin, protoporphyrin IX,tetra-(4-N-carboxyphenyl)-porphine, tetra-(3-methoxyphenyl)-porphine,tetra-(3-methoxy-2,4-difluorophenyl)-porphine,5,10,15,20-tetrakis(4-N-methylpyridyl)porphine,tetra-(4-N-methylpyridyl)-porphine tetrachloride,tetra-(3-N-methylpyridyl)-porphine, tetra-(2-N-methylpyridyl)-porphine,tetra(4-N,N,N-trimethylanilinium)porphine,tetra-(4-N,N,N″-trimethylamino-phenyl)porphine tetrachloride,tetranaphthaloporphyrin, tetraphenylporphyrin,tetra-(4-sulfonatophenyl)-porphine, 4-sulfonatophenylporphine,uroporphyrin, uroporphyrin III, uroporphyrin IX, and uroporphyrin I, andesters thereof.

In some embodiments, a porphyrin compound may be an ester selected fromthe group consisting of 5-azaprotoporphyrin dimethylester,coproporphyrin III tetramethylester, deuteroporphyrin IX dimethylester,diformyl deuteroporphyrin IX dimethylester, hematoporphyrin IXdimethylester, mesoporphyrin dimethylester, mesoporphyrin IXdimethylester, monoformyl-monovinyl-deuteroporphyrin IX dimethylester,protoporphyrin dimethylester, and protoporphyrin IX dimethylester.

In some embodiments, a porphyrin compound may be selected from the groupconsisting of coproporphyrin III, coproporphyrin III tetramethylester,deuteroporphyrin, deuteroporphyrin IX dichloride, deuteroporphyrin IXdimethylester, hematoporphyrin, hematoporphyrin IX, hematoporphyrinderivative, hematoporphyrin derivative A, hematoporphyrin IXdihydrochloride, hematoporphyrin dihydrochloride, hematoporphyrin IXdimethylester, mesoporphyrin, mesoporphyrin dimethylester, mesoporphyrinIX, mesoporphyrin IX dimethylester, protoporphyrin, protoporphyrin IX,protoporphyrin dimethylester, protoporphyrin IX dimethylester,uroporphyrin, uroporphyrin III, uroporphyrin IX, and uroporphyrin I.

For example, a porphyrin compound may include protoporphyrin IX,deuteroporphyrin IX dichloride, deuteroporphyrin IX dimethylester,hematoporphyrin, hematoporphyrin IX, hematoporphyrin derivative,mesoporphyrin dimethylester, mesoporphyrin IX, or mesoporphyrin IXdimethylester.

According to some embodiments, a porphyrin compound may compriseprotoporphyrin IX:

In some embodiments, a conjugated fused tricyclic compound of FormulasI, II, and/or III (e.g., II(a), II(b), II(d), II(e), II(c)) may beincluded in a cosmetic or dermatological composition for coating a skinsurface to protect the skin from getting damaging amounts of singletoxygen when skin cell-contained or blood-contained porphyrin compounds(e.g., protoporphyrin IX), are exposed to sunlight, or other visiblelight.

A dibenzoylmethane derivative may be selected from the group consistingof 2-methyldibenzoylmethane; 4-methyldibenzoylmethane;4-isopropyldibenzoylmethane; 4-tert-butyldibenzoylmethane;2,4-dimethydibenzoylmethane; 2-5-dimethydibenzoylmethane;4,4′-diispropyldibenzoylmethane; 4,4′-dimethoxydibenzoylmethane;4-tert-butyl-4′-methoxdibenzoylmethane;2-methyl-5-isopropy-4′-methoxydibenzoylmethane;2-methyl-5-tert-butyl-4′-methoxydibenzoylmethane;2,4-dimethyl-4′-methoxydibenzoymethane;2,6-dimethyl-4-tert-butyl-4′-methoxydibenzolmthane, and combinationsthereof. A compound according to Formulas I, II, and/or III may alsophotostabilize retinoids, coenzyme Q, cholecalciferol, and/orresveratrol.

In some embodiments, a sunscreen, cosmetic or dermatological compositiondescribed herein may comprise one or more fused tricyclic compounds aswell as one or more UV-absorbing, chromophore-containing compounds. Forexample, a composition may include both UV-A and UV-B photoactivecompounds in a cosmetically acceptable carrier, optionally includingadditives, such as emollients, stabilizers, emulsifiers, andcombinations thereof. These additives may be used in preparing a UVfilter composition in an emulsion (oil-in-water or water-in-oil) from acomposition that includes one or more photoactive compounds and asolvent or a solvent combination that includes one or more organicsolvents and water. When made, an emulsion may be an oil-in-wateremulsion, wherein the oil phase is primarily formed from a mixture ofthe UV filter compound(s) including, for example, a dibenzoylmethanederivative, such as Avobenzone, and one or more organic solvents.

A photoactive composition may include one or more photoactive compounds,wherein the photoactive compound(s) act to absorb UV radiation andthereby protect the substrate (e.g., human skin, resins, films, and thelike) from the harmful effects of UV radiation. Absorption may cause aphotoactive compound to reach an excited state, wherein the excitedstate is characterized by the presence of excited electronic energy(e.g., singlet state energy or triplet state energy), as compared to theground state of the photoactive compound. Once a photoactive compoundreaches an excited state there exists a number of pathways by which theexcited photoactive compound can dissipate its excess energy (e.g.,singlet and/or triplet energy), however, many of those pathwaysadversely affect the ability of the photoactive compound to furtherabsorb UV radiation. Conjugated fused polycyclic molecules may acceptelectronic singlet excited state energy from UV-absorbers, such asAvobenzone, octyl methoxycinnamate (Octinoxate), and octyl salicylate(Octisalate). Conjugated fused polycyclic compounds may be effective UVAabsorbers in addition to providing electronic singlet state energyquenching of other UV-absorbing compounds in sunscreen, cosmetic anddermatological compositions. In some embodiments, the efficacy ofconjugated fused polycyclic molecules may be enhanced (e.g.,synergistically enhanced) when combined with one or more additionalelectronic singlet excited state quenching compounds such as oxybenzoneand/or an alkoxy crylene. Photostabilization may be achieved insunscreen compositions containing conjugated fused polycyclic moleculesdescribed herein together with octyl methoxycinnamate and Avobenzone.

A photoactive compound is one that responds to light (e.g., visible, UVlight) photoelectrically. For example, photoactive compound-containingcompositions that respond to UV radiation photoelectrically byphotoactive compound photodegradation may benefit by the inclusion ofconjugated fused polycyclicmolecules described herein. Conjugated fusedpolycyclic compounds, according to some embodiments, are usefulphotostabilizers and/or photoactive compounds when combined with anysingle or combination of photoactive compounds.

In some embodiments, a photoactive compound may be selected from thegroup consisting of p-aminobenzoic acid and salts and derivativesthereof; anthranilate and derivatives thereof; salicylate andderivatives thereof; cinnamic acid and derivatives thereof;dihydroxycinnamic acid and derivatives thereof; camphor and salts andderivatives thereof; trihydroxycinnamic acid and derivatives thereof;dibenzalacetone naptholsulfonate and salts and derivatives thereof;benzalacetophenone naphtholsulfonate and salts and derivatives thereof;dihydroxy-naphthoic acid and salts thereof; o-hydroxydiphenyldisulfonateand salts and derivatives thereof; p-hydroxdydiphenyldisulfonate andsalts and derivatives thereof; coumarin and derivatives thereof; diazolederivatives; quinine derivatives and salts thereof; quinolinederivatives; hydroxyl-substituted benzophenone derivatives; naphthalatederivatives; methoxy-substituted benzophenone derivatives; uric acidderivatives; vilouric acid derivatives; tannic acid and derivativesthereof; hydroquinone; benzophenone derivatives; 1,3,5-triazinederivatives; phenyldibenzimidazole tetrasulfonate and salts andderivatives thereof; terephthalyidene dicamphor sulfonic acid and saltsand derivatives thereof; methylene bis-benzotriazolyltetramethylbutylphenol and salts and derivatives thereof;bis-ethylhexyloxyphenol methoxyphenyl triazine and salts, diethylaminohydroxyl benzoyl and derivatives thereof; and combinations of theforegoing.

A cosmetic or dermatological composition may include a cinnamate ester,such as 2-ethylhexyl p-methoxycinnamate, isoamyl p-methoxycinnamate, anda combination thereof. For example, a cinnamate ester may be2-ethylhexyl p-methoxycinnamate. In some embodiments, a cinnamate estermay be present in the composition in an amount in a range of about 0.1wt. % to about 15 wt. %, based on the total weight of the composition.

The cosmetic or dermatological composition also may include about 0.1 toabout 10 wt. % of a triplet quencher selected from the group consistingof octocrylene, methyl benzylidene camphor, diethylhexyl2,6-naphthalate, and combinations thereof.

In some embodiments, a cosmetic or dermatological composition may alsoinclude a UVA filter and/or UVB filter compound and/or a broad-bandfilter compound for protection of the skin from UVA and/or UVBwavelengths. Photostability is a problem with all UV filters becausethey all reach an electronic singlet excited state upon exposure to UVradiation. According to some embodiments, filters that may bephotostabilized by a conjugated fused polycyclic molecule may includep-aminobenzoic acid, its salts and its derivatives (e.g., ethyl,isobutyl, glyceryl esters, p-dimethylaminobenzoic acid); anthranilates(e.g., o-aminobenzoates, methyl, menthyl, phenyl, benzyl, phenylethyl,linalyl, terpinyl, and cyclohexenyl esters); salicylates (e.g., octyl,amyl, phenyl, benzyl, menthyl (homosalate), glyceryl, anddipropyleneglycol esters); cinnamic acid derivatives (e.g., menthyl andbenzyl esters, alpha-phenyl cinnamonitrile, butyl cinnamoyl pyruvate);dihydroxycinnamic acid derivatives (e.g., umbelliferone,methylumbelliferone, methylaceto-umbelliferone); camphor derivatives(e.g., 3 benzylidene, 4 methylbenzylidene, polyacrylamidomethylbenzylidene, benzalkonium methosulfate, benzylidene camphor sulfonicacid, and terephthalylidene dicamphor sulfonic acid); trihydroxycinnamicacid derivatives (e.g., esculetin, methylesculetin, daphnetin, and theglucosides, esculin and daphnin); hydrocarbons (e.g., diphenylbutadiene,stilbene); dibenzalacetone; benzalacetophenone; naphtholsulfonates(e.g., sodium salts of 2-naphthol-3,6-disulfonic and of2-naphthol-6,8-disulfonic acids); dihydroxy-naphthoic acid and itssalts; o- and p-hydroxydiphenyldisulfonates; coumarin derivatives (e.g.,7-hydroxy, 7-methyl, 3-phenyl); diazoles (e.g.,2-acetyl-3-bromoindazole, phenyl benzoxazole, methyl naphthoxazole,various aryl benzothiazoles); quinine salts (e.g., bisulfate, sulfate,chloride, oleate, and tannate); quinoline derivatives (e.g.,8-hydroxyquinoline salts, 2-phenylquinoline); hydroxy- ormethoxy-substituted benzophenones; uric acid derivatives; vilouric acidderivatives; tannic acid and its derivatives; hydroquinone; andbenzophenones (e.g., oxybenzone, sulisobenzone, dioxybenzone,benzoresorcinol, octabenzone, 4-isopropyldibenzoylmethane,butylmethoxydibenzoylmethane, etocrylene, and4-isopropyl-dibenzoylmethane). For example, UV filters that may bephotostabilized by a conjugated fused polycyclic molecule may include2-ethylhexyl p-methoxycinnamate, 4,4′-t-butyl methoxydibenzoylmethane,octyldimethyl p-aminobenzoate, digalloyltrioleate, ethyl4-[bis(hydroxypropyl)]aminobenzoate, 2-ethylhexylsalicylate, glycerolp-aminobenzoate, 3,3,5-trimethylcyclohexylsalicylate, and combinationsthereof.

Photoactive compositions disclosed herein may include one or morephotoactive compounds, according to some embodiments. For example, aphotoactive composition may comprise one or more UV-A photoactivecompounds and one or more UV-B photoactive compounds. A sunscreencomposition may include a photoactive compound selected from the groupconsisting of p-aminobenzoic acid and salts and derivatives thereofanthranilate and derivatives thereof; dibenzoylmethane and derivativesthereof; salicylate and derivatives thereof; cinnamic acid andderivatives thereof; dihydroxycinnamic acid and derivatives thereof;camphor and salts and derivatives thereof; trihydroxycinnamic acid andderivatives thereof; dibenzalacetone naphtholsulfonate and salts andderivatives thereof; benzalacetophenone naphtholsulfonate and salts andderivatives thereof; dihydroxy-naphthoic acid and salts thereof;o-hydroxydiphenyldisulfonate and salts and derivatives thereof;p-hydroxydiphenyldisulfonate and salts and derivatives thereof; coumarinand derivatives thereof; diazole derivatives; quinine derivatives andsalts thereof; quinoline derivatives; uric acid derivatives; vilouricacid derivatives; tannic acid and derivatives thereof; hydroquinone;diethylamino hydroxybenzoyl hexyl benzoate and salts and derivativesthereof; and combinations of the foregoing.

UV A radiation (about 320 nm to about 400 nm), is recognized ascontributing to causing damage to skin, particularly to very lightlycolored or sensitive skin. A sunscreen composition may include a UV-Aphotoactive compound (e.g., a dibenzoylmethane derivative UV-Aphotoactive compound). Examples of a UV-A absorbing dibenzoylmethanederivative may include include, 2-methyldibenzoylmethane;4-methyldibenzoylmethane; 4-isopropyldibenzoylmethane;4-tert-butyldibenzoylmethane; 2,4-dimethyldibenzoylmethane;2,5-dimethyldibenzoylmethane; 4,4′-diisopropyldibenzoylmethane;4,4′-dimethoxydibenzoylmethane; 4-tert-butyl-4′-methoxydibenzoylmethane;2-methyl-5-isopropyl-4′-methoxydibenzoylmethane;2-methyl-5-tert-butyl-4′-methoxydibenzoylmethane;2,4-dimethyl-4′-methoxydibenzoylmethane;2,6-dimethyl-4-tert-butyl-4′-methoxydibenzoylmethane, and combinationsthereof.

For a product marketed in the United States, cosmetically acceptablephotoactive compounds and concentrations (reported as a percentage byweight of the total cosmetic sunscreen composition) may include:aminobenzoic acid (also called para aminobenzoic acid and PABA; 15% orless), Avobenzone (also called butyl methoxy dibenzoylmethane; 3% orless), cinoxate (also called 2 ethoxyethyl p methoxycinnamate; 3% orless), dioxybenzone (also called benzophenone 8; 3% or less), homosalate((also called 3,3,5-trimethylcyclohexyl salicylate, 15% or less),menthyl anthranilate (also called menthyl 2 aminobenzoate; 5% or less),octocrylene (also called 2 ethylhexyl 2 cyano 3,3 diphenylacrylate; 10%or less), octyl methoxycinnamate (7.5% or less), octyl salicylate (alsocalled 2 ethylhexyl salicylate; 5% or less), oxybenzone (also calledbenzophenone 3; 6% or less), padimate O (also called octyl dimethylPABA; 8% or less), phenylbenzimidazole sulfonic acid (water soluble; 4%or less), sulisobenzone (also called benzophenone 4; 10% or less),titanium dioxide (25% or less), trolamine salicylate (also calledtriethanolamine salicylate; 12% or less), and zinc oxide (25% or less).

Other cosmetically acceptable photoactive compounds and concentrations(percent by weight of the total cosmetic sunscreen composition) mayinclude diethanolamine methoxycinnamate (10% or less),ethyl-[bis(hydroxypropyl)]aminobenzoate (5% or less), glycerylaminobenzoate (3% or less), 4 isopropyl dibenzoylmethane (5% or less), 4methylbenzylidene camphor (6% or less), terephthalylidene dicamphorsulfonic acid (10% or less), and sulisobenzone (also called benzophenone4, 10% or less).

For a product marketed in the European Union, cosmetically acceptablephotoactive compounds and concentrations (reported as a percentage byweight of the total cosmetic sunscreen composition) may include: PABA(5% or less), camphor benzalkonium methosulfate (6% or less), homosalate(10% or less), benzophenone 3 (10% or less), phenylbenzimidazolesulfonic acid (8% or less, expressed as acid), terephthalidene dicamphorsulfonic acid (10% or less, expressed as acid), butylmethoxydibenzoylmethane (5% or less), benzylidene camphor sulfonic acid(6% or less, expressed as acid), octocrylene (10% or less, expressed asacid), polyacrylamidomethyl benzylidene camphor (6% or less), ethylhexylmethoxycinnamate (10% or less), PEG 25 PABA (10% or less), isoamyl pmethoxycinnamate (10% or less), ethylhexyl triazone (5% or less),drometrizole trielloxane (15% or less), diethylhexyl butamido triazone(10% or less), 4 methylbenzylidene camphor (4% or less), 3 benzylidenecamphor (2% or less), ethylhexyl salicylate (5% or less), ethylhexyldimethyl PABA (8% or less), benzophenone 4 (5%, expressed as acid),methylene bis benztriazolyl tetramethylbutylphenol (10% or less),disodium phenyl dibenzimidazole tetrasulfonate (10% or less, expressedas acid), bis ethylhexyloxyphenol methoxyphenol triazine (10% or less),methylene bisbenzotriazolyl tetramethylbutylphenol (10% or less, alsocalled TINOSORB M or Bisoctrizole), and bisethylhexyloxyphenolmethoxyphenyl triazine. (10% or less, also called TINOSORB S orBemotrizinol).

Addition of polar solvents to the oil phase of a composition may, insome embodiments, increase the photostability of photoactive compounds(e.g., in a sunscreen composition). In some embodiments, a sunscreencomposition may comprise one or more highly polar solvents in theoil-phase of the composition. For example, a sufficient amount of apolar solvent may be present in a sunscreen composition to raise thedielectric constant of the oil-phase of the composition to a dielectricconstant of at least about 7 (e.g., at least about 8).

A photoactive compound may be considered stable when, for example, after30 MED irradiation the photoactive compound has retained at least about90% of its original absorbance at a wavelength, or over a range ofwavelengths of interest (e.g., the wavelength at which a photoactivecompound has a peak absorbance, such as 350-370 nm for Avobenzone).Likewise, a sunscreen composition may include a plurality of photoactivecompounds and a sunscreen composition, as a whole, may be consideredstable when, for example, after 30 MED irradiation the sunscreencomposition has retained at least about 90% of its original absorbanceat one or more wavelengths of interest (e.g., at or near the peakabsorbance wavelength of the primary photoactive compound).

According to some embodiments, a conjugated fused polycyclic moleculemay be included in a sunscreen, cosmetic or dermatological formulationwith a water soluble UV filter compound and/or a broad-band filtercompound. A cosmetic or dermatological formulation optionally mayfurther include a dibenzoylmethane derivative and/or a dialkylnaphthalate.

Water-soluble UV filter substances may include, in some embodiments,sulfonated UV filters. For example, water-soluble UV filter substancesmay include:

phenylene-1,4-bis(2-benzimidazyl)-3,3′-5,5′-tetrasulfonic acid, whichhas the following structure:

and its salts, especially the corresponding sodium, potassium ortriethanolammonium salts, in particularphenylene-1,4-bis(2-benzimidazyl)-3,3′-5,5′-tetrasulfonic acid bissodiumsalt

with the INCI name disodium phenyl dibenzimidazole tetrasulfonate (CASNo.: 180898-37-7), which is obtainable for example under the proprietaryname Neo Heliopan A P from Haarmann & Reimer.

Examples of sulfonated UV filters may include salts of2-phenylbenzimidazole-5-sulfonic acid, such as its sodium, potassium orits triethanolammonium salts, and the sulfonic acid itself

with the INCI name phenylbenzimidazole sulfonic acid (CAS No.27503-81-7), which is obtainable for example under the proprietary nameEusolex 232 from Merck or under Neo Heliopan Hydro from Haarmann &Reimer.

Water-soluble UV B and/or broad-band filter substances may include, insome embodiments, sulfonic acid derivatives of 3-benzylidenecamphor,such as, for example, 4-(2-oxo-3-bornylidenemethyl)benzene-sulfonicacid, 2-methyl-5-(2-oxo-3-bornylidenemethyl)sulfonic acid and the saltsthereof.

The total amount of one or more water-soluble UV filter substances inthe finished cosmetic or dermatological preparations may be chosen fromthe range 0.01% by weight to about 20% by weight, from about 0.1 toabout 20% by weight, or from about 0.1% to about 10% by weight, in eachcase based on the total weight of the composition.

According to some embodiments, a conjugated fused polycyclic moleculeaccording to Formulas I, II, and/or III(e.g., I(a), I(a)(1), II(a),II(a)(1), II(b), II(b)(1), II(d), II(d)(1), II(e), II(e)(1), II(c),II(c)(1), and combinations thereof) may be included in sunscreen,cosmetic or dermatological formulation with a hydroxybenzophenonecompound and/or a broad-band filter compound and optionally togetherwith a dibenzoylmethane derivative and/or a dialkyl naphthalate.

According to some embodiments, a composition having a conjugated fusedpolycyclic molecule may have no need to comprise (e.g., may exclude)other UV photostabilizers.

A hydroxybenzophenone may have the following structural formula:

where R¹ and R² independent of one another are hydrogen, C₁ C₂₀-alkyl,C₃-C₁₀-cycloalkyl or C₃-C₁₀-cyloalkenyl, wherein the substituents R¹ andR² together with the nitrogen atom to which they are bound can form a 5-or 6-ring and R³ is a C₁-C₂0 alkyl radical.

For example, a hydroxybenzophenone may comprise2-(4′-diethylamino-2′-hydroxybenzoyl)benzoic acid hexyl ester (also:aminobenzophenone) having the structure

and is available from BASF under the Uvinul A Plus.

According to some embodiments, sunscreen, cosmetic or dermatologicalpreparations may comprise 0.1 to 20% by weight, 0.1 to 15% by weight,and/or 0.1 to 10% by weight, of one or more hydroxybenzophenones.

According to some embodiments, sunscreen, cosmetic or dermatologicalpreparations may comprise about 0.001% to about 30% by weight, about0.01% to about 20% by weight, and/or about 0.5 to about 15% by weight,of one or more dialkyl naphthalates available, for example, under thetrade name Hallbrite TQ™ from HallStar Innovaction Corp. or Corapan TQ™from H&R. Dialkyl naphthalates may comprise branched alkyl groups with 6to 10 carbon atoms

According to some embodiments, a

cosmetic or dermatological light-protection composition may beformulated for use as a sunscreen, cosmetic or dermatologicallight-protection material and one or more additional purposes including,for example, treatment, care and cleansing of the skin and/or hair andas a cosmetic product in decorative cosmetics.

In some embodiments, a conjugated fused polycyclic molecule may beincluded in a composition with a benzotriazole derivative compoundand/or a broad-band filter compound and optionally, together with adibenzoylmethane derivative and/or a dialkyl naphthalate. An example ofa benzotriazole derivative is2,2′-methylenebis(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)phenol),which has the chemical structural formula

(INCL: bisoctyltriazole). It is obtainable under the proprietary nameTinosorb® from CIBA-Chemikalien GmbH and is distinguished by good UVabsorption properties. The disadvantage of this substance is thecharacteristic of forming imperceptibly thin films on the skin whichhave unpleasant tactile properties.

According to some embodiments, a UV filter compound that may be includedin a composition may be selected from UV filter compounds disclosed inpublished PCT application WO 2009/020676, hereby incorporated byreference (e.g., water-soluble, organic and particulate UV filtercompounds).

In some embodiments, a UV filter compound may be a benzotriazle compoundhaving the structure

Particulate UV filter substances may include inorganic pigments. In someembodiments, inorganic pigments may include, for example, metal oxidesand/or other metal compounds which are slightly soluble or insoluble inwater. For example, an inorganic pigment may include oxides of titanium(TiO₂), zinc (ZnO), iron (e.g. Fe₂O₃), zirconium (ZrO₂), silicon (SiO₂),manganese (e.g. MnO), aluminum (Al₂O₃), cerium (e.g. Ce₂O₃), mixedoxides of the corresponding metals, and mixtures of such oxides, and thesulfate of barium (BaSO₄).

Zinc oxides may be used in the form of oily or aqueous predispersions.Zinc oxide particles and predispersions of zinc oxide particles whichare suitable according to the disclosure may be distinguished by aprimary particle size of <300 nm. Zinc oxide may include, for example,Z-Cote HP1 and Z-Cote from BASF and zinc oxide NDM from Haarmann &Reimer.

In some embodiments, titanium dioxide pigments may be in the form ofboth the rutile and anatase crystal modification and/or may besurface-treated (“coated”), for example, to form or retain ahydrophilic, amphiphilic or hydrophobic character. This surfacetreatment may consist of providing the pigments with a thin hydrophilicand/or hydrophobic inorganic and/or organic layer. The various surfacecoatings may contain water.

Inorganic surface coatings, in some embodiments, may comprise aluminumoxide (Al₂O₃), aluminum hydroxide Al(OH)₃ or aluminum oxide hydrate(also: alumina, CAS No.: 1333-84-2), sodium hexametaphosphate (NaPO₃)₆,sodium metaphosphate (NaPO₃)_(n), silicon dioxide (SiO₂) (also: silica,CAS No.: 7631-86-9), or iron oxide (Fe₂O₃). These inorganic surfacecoatings may occur alone, in combination and/or in combination withorganic coating materials.

Organic surface coatings, in some embodiments, may include one or morepolymeric materials. Some examples of polymeric materials may includepolyacrylate, polystyrene, polyester, polyurethanes, and copolymersthereof. These organic surface coatings may occur alone, in combinationand/or in combination with inorganic coating materials.

Coated and uncoated titanium dioxides may be used in the form of oily oraqueous predispersions. In some embodiments, dispersion aids and/orsolubilization mediators may be included.

According to some embodiments, a titanium dioxide may have a primaryparticle size of about 10 nm to about 150 nm. Examples of a titaniumdioxide may include MT-100 Z and MT-100 TV from Tayca Corporation,Eusolex T-2000 from Merck and titanium dioxide T 805 from Degussa.

In some embodiments, pigments may comprise latex particles. Latexparticles may include those described in the following publications:U.S. Pat. No. 5,663,213 and EP 0 761 201. Latex particles may be formedfrom water and styrene/acrylate copolymers (e.g., “Alliance SunSphere”from Rohm & Haas).

A compositions, according to some embodiments, may include one or moreantioxidants. A composition may include any desired antioxidant, forexample, an antioxidant suitable or conventional for cosmetic and/ordermatological applications.

An antioxidants may be selected, according to some embodiments, fromamino acids (e.g. glycine, histidine, tyrosine, tryptophan) andderivatives thereof, imidazoles (e.g. urocanic acid) and derivativesthereof, peptides such as D,L-camosine, D-carnosine, L-carnosine andderivatives thereof (e.g. anserine), carotenoids, carotenes (e.g.α-carotene, β-carotene, lycopene) and derivatives thereof, chlorogenicacid and derivatives thereof, lipoic acid and derivatives thereof (e.g.dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols(e.g. thioredoxin, glutathione, cysteine, cystine, cystamine and theglycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl,palmitoyl, oleyl, .gamma.-linoleyl, cholesteryl and glyceryl estersthereof) and salts thereof, dilauryl thiodipropionate, distearylthiodipropionate, thiodipropionic acid and derivatives thereof (esters,ethers, peptides, lipids, nucleotides, nucleosides and salts) andsulfoximine compounds (e.g. buthionine sulfoximines, homocysteinesulfoximine, buthionine sulfones, penta-, hexa-, heptathioninesulfoximine) in very low tolerated doses (e.g. pmol to μmol/kg), andalso (metal) chelating agents (e.g. α-hydroxy fatty acids, palmiticacid, phytic acid, lactoferrin), α-hydroxy acids (e.g. citric acid,lactic acid, malic acid), humic acid, bile acid, bile extracts,bilirubin, biliverdin, EDTA, EGTA and derivatives thereof, unsaturatedfatty acids and derivatives thereof (e.g. .gamma.-linolenic acid,linoleic acid, oleic acid), folic acid and derivatives thereof,ubiquinone and ubiquinol and derivatives thereof, vitamin C andderivatives (e.g. ascorbyl palmitate, Mg ascorbyl phosphate, ascorbylacetate), tocopherols and derivatives (e.g. vitamin E acetate), vitaminA and derivatives (vitamin A palmitate) and coniferyl benzoate of gumbenzoin, rutinic acid and derivatives thereof, α-glycosylrutin, ferulicacid, furfurylideneglucitol, carnosine, butylhydroxytoluene,butylhydroxyanisole, nordihydroguaiaretic acid,trihydroxybutyro-phenone, uric acid and derivatives thereof, mannose andderivatives thereof, zinc and derivatives thereof (e.g. ZnO, ZnSO₄),selenium and derivatives thereof (e.g. selenomethionine), stilbenes andderivatives thereof (e.g. stilbene oxide, trans-stilbene oxide) and thederivatives (salts, esters, ethers, sugars, nucleotides, nucleosides,peptides and lipids) of said active ingredients, which may be suitableaccording to some embodiments of the disclosure.

Thus, in some embodiments, a cosmetic or dermatological composition mayinclude one or more oxidation-sensitive or UV-sensitive ingredientsselected from the group consisting of retinoid compounds, coenzyme Q,cholecalciferol, resveratrol, carotenoid compounds, lipoic acid andderivatives thereof, vitamin E and derivatives thereof, vitamin F andderivatives thereof, and dioic acid in an amount from about 0.0001 wt %to about 10 wt %, based on the total weight of the composition.

In some embodiments, hydrophilic active ingredients (individually or inany combinations with one another) may be stabilized by their usetogether with one or more conjugated fused tricyclic compounds. Examplesof hydrophilic active ingredients may include include biotin; carnitineand derivatives; creatine and derivatives; folic acid; pyridoxine;niacinamide; polyphenols (flavonoids, alpha-glucosylrutin); ascorbicacid and derivatives; Hamamelis; Aloe Vera; panthenol; and amino acids.In some embodiments, hydrophilic active ingredients may includewater-soluble antioxidants, such as, for example, vitamins.

The amount of hydrophilic active ingredients (one or more compounds) inthe preparations may be about 0.0001 to about 10% by weight (e.g., about0.001 to about 5% by weight), based on the total weight of thepreparation.

According to some embodiments, a composition may include one or moreantioxidants. Examples of antioxidants may include all antioxidantscustomary or suitable for cosmetic and/or dermatological applications.The amount of antioxidants (one or more compounds) in the preparationsmay be about 0.001 to about 30% by weight, about 0.05 to about 20% byweight, about 0.1 to about 10% by weight, based on the total weight ofthe preparation.

The respective concentrations of vitamin E and/or derivatives thereofmay be selected, in some embodiments, from the range about 0.001% toabout 10% by weight, based on the total weight of the Formulation.According to some embodiments, the respective concentrations of vitaminA or vitamin A derivatives, or carotenes or derivatives thereof may beselected from the range from 0.001 to 10% by weight, based on the totalweight of the formulation, according to some embodiments.

In some embodiments, a cosmetic preparation may comprise one or morecosmetic or dermatological active ingredients. Active ingredients mayinclude, for example, antioxidants which may protect the skin againstadditional oxidative stress, natural active ingredients and/orderivatives thereof. Examples of active ingredients may include, forexample, ubiquinones, retinoids, carotenoids, creatine, taurine and/orβ-alanine.

Formulations, according to some embodiments of the disclosure, maycomprise antiwrinkle active ingredients. For example, a formulation maycomprise an antiwrinkle active ingredient selected from flavoneglycosides (e.g., α-glycosylrutin), coenzyme Q10, vitamin E and/orderivatives and the like. Formulations comprising an antiwrinkle activeingredient may be suitable for the prophylaxis and/or treatment ofcosmetic or dermatological changes in skin. Skin changes may include,for example changes that arise, for example, during skin aging.Formulations with an antiwrinkle active ingredient may be suitable forthe prophylaxis and/or treatment of conditions including, for example,dryness, roughness and formation of dryness wrinkles, itching, reducedrefatting (e.g. after washing), visible vascular dilations(teleangiectases, couperosis), flaccidity and formation of wrinkles andlines, local hyperpigmentation, hypopigmentation and abnormalpigmentation (e.g., age spots), increased susceptibility to mechanicalstress (e.g., cracking) and the like.

In some embodiments, cosmetic or dermatological compositions may includetriazines, benzotriazoles, latex particles, organic pigments, inorganicpigments, and mixtures thereof.

A cosmetic or dermatological compositions may include conventionaladditives and solvents used for the treatment, care and cleansing ofskin and/or the hair and as a make-up product in decorative cosmetics.

For use in protecting skin from oxidative stress, a cosmetic and/ordermatological compositions may contain about 0.01 wt. % to about 20 wt.% cyano-containing fused tricyclic compound(s) and the composition maybe applied to the skin and/or the hair in a sufficient quantity in themanner customary for cosmetics.

A cosmetic and dermatological compositions described herein may comprisecosmetic auxiliaries such as those conventionally used in suchpreparations, e.g. preservatives, bactericides, perfumes, antifoams,dyes, pigments which have a coloring effect, thickeners, moisturizersand/or humectants, fats, oils, waxes or other conventional constituentsof a cosmetic or dermatological Formulation, such as alcohols, polyols,polymers, foam stabilizers, electrolytes, organic solvents or siliconederivatives.

The present disclosure relates, in some embodiments, to articles thatmay include a conjugated fused polycyclic molecule. Some examples of anarticle may include buildings, bridges, automobiles, appliances, boats,fabrics (e.g., garments), signs, and sports equipment (e.g., nets,balls, boards, flags). An article may be combined with a conjugatedfused polycyclic molecule during manufacture or synthesis, according tosome embodiments. A conjugated fused polycyclic molecule (e.g., acomposition comprising a conjugated fused polycyclic molecule) may beapplied to an article after it is formed.

The present disclosure relates, in some embodiments, systems forresolution of an excited energy state. A system may comprise, forexample, a donor molecule (e.g., a porphyrin according to Formula IV)and/or an acceptor molecule (e.g., a polycyclic molecule according toFormula I or II).

In some embodiments, the disclosure relates to a method of suppressingthe generation of singlet oxygen and/or other reactive oxygen species orradicals by an excited donor molecule (e.g., porphyrin, mammalianporphyrin). A method may include contacting an acceptor molecule with adonor molecule in any desired milieu. A method may include suppressingthe formation of free radical oxygen, superoxide anion, peroxide,hydroxyl radical, and/or hydroxyl ion, in some embodiments.

In some embodiments, the disclosure relates to a method of quenchingexcited state energy from a pigment and/or porphyrin compound that hasbeen excited by exposure to and absorption of light (e.g., having awavelength in the wavelength range of 380-800 nm), comprising contacting(e.g., reacting) a pigment and/or porphyrin compound comprising aporphyrin moiety of Formula IV or a derivative or tautomer thereof witha polycyclic molecule according to Formula I or Formula II.

The disclosure further relates, according to some embodiments, to amethod of protecting skin from oxidative stress caused by the generationof free radical oxygen comprising coating at least a portion of the skinwith a porphyrin excited state quencher capable of accepting or donatingan electron from or to a porphyrin compound in the excited state andreturning the excited porphyrin compound to its ground state, saidporphyrin quencher comprising a molecule according to Formulas I, II,and/or II.

In some embodiments, the disclosure relates to a method of quenchingexcited state energy from a porphyrin compound that has been excited byexposure to and absorption of light (e.g., having a wavelength in thewavelength range of 380-800 nm), comprising contacting (e.g., reacting)a porphyrin compound comprising a porphyrin moiety of Formula IV or aderivative or tautomer thereof with a polycyclic molecule according toFormula I or Formula II.

Excited states of porphyrins may be harnessed to administer photodynamictherapy (PDT). Protoporphyrin IX (C₃₄H₃₄N₄O₄) is used in PDT, forexample, as a treatment for basal cell carcinoma (BCC), which is themost common form of skin cancer in humans. The PDT treatment involvesapplying a photosensitizer precursor, such as aminolevulinic acid (ALA)to the cancerous cells, waiting a few hours for the ALA to be taken upby the cells and converted to protoporphyrin IX, and then irradiatingthe cancerous cells with light in the wavelength of about 380 to about650 nm. This illumination excites the protoporphyrin IX to a singletexcited state, after which it intersystem crosses to a triplet excitedstate, thereby making it reactive with oxygen. Consequently, cytotoxicsinglet oxygen is generated that kills cancerous and pre-cancerouscells. To mitigate potentially adverse effects of PDT onnon-carcinogenic cells, a molecule having Formula I or Formula II may becontacted with the cells to be protected.

In some embodiments, the disclosure relates to a method of protectinghealthy cells adjacent to cancerous or pre-cancerous cells undergoingphotodynamic therapy comprising applying a composition comprising anacceptor molecule (e.g., an acceptor according to Formulas I, II, and/orFormula III) to said adjacent cells to reduce the generation of freeradical oxygen from said healthy cells while the photodynamic therapygenerates free radical oxygen from said cancerous or pre-cancerouscells. In some embodiments, a composition may further comprise aporphyrin excited state quencher compound comprising a porphyrin moietyof Formula IV or a derivative or tautomer thereof.

Conjugated fused polycyclic molecules may be accessible through acondensation reaction between a carboxyl compound and an active hydrogencontaining compound. Examples of such methods appear in the Examplesbelow.

As will be understood by those skilled in the art who have the benefitof the instant disclosure, other equivalent or alternative compositions,objects, methods, and systems for quenching, dissipating, and/orotherwise resolving excited state energy can be envisioned withoutdeparting from the description contained herein. Accordingly, the mannerof carrying out the disclosure as shown and described is to be construedas illustrative only.

Persons skilled in the art may make various changes in the kind, number,and/or arrangement of R-groups, substituents, and/or heteroatoms withoutdeparting from the scope of the instant disclosure. In addition, thesize of an object and/or system may be scaled up or down to suit theneeds and/or desires of a practitioner. Each disclosed method and methodstep may be performed in association with any other disclosed method ormethod step and in any order according to some embodiments. Where theverb “may” appears, it is intended to convey an optional and/orpermissive condition, but its use is not intended to suggest any lack ofoperability unless otherwise indicated. Persons skilled in the art maymake various changes in methods of preparing and using a composition,device, and/or system of the disclosure. For example, a composition,object, and/or system may be prepared and or used as appropriate foranimal and/or human use (e.g., with regard to sanitary, infectivity,safety, toxicity, biometric, and other considerations). Elements,compositions, objects, systems, methods, and method steps not recitedmay be included or excluded as desired or required.

Also, where ranges have been provided, the disclosed endpoints may betreated as exact and/or approximations as desired or demanded by theparticular embodiment. Where the endpoints are approximate, the degreeof flexibility may vary in proportion to the order of magnitude of therange. For example, on one hand, a range endpoint of about 50 in thecontext of a range of about 5 to about 50 may include 50.5, but not 52.5or 55 and, on the other hand, a range endpoint of about 50 in thecontext of a range of about 0.5 to about 50 may include 55, but not 60or 75. In addition, it may be desirable, in some embodiments, to mix andmatch range endpoints. Also, in some embodiments, each figure disclosed(e.g., in one or more of the examples, tables, and/or drawings) may formthe basis of a range (e.g., depicted value +/−about 10%, depicted value+/−about 50%, depicted value +/−about 100%) and/or a range endpoint.With respect to the former, a value of 50 depicted in an example, table,and/or drawing may form the basis of a range of, for example, about 45to about 55, about 25 to about 100, and/or about 0 to about 100.Disclosed percentages are weight percentages except where indicatedotherwise.

All or a portion of an object and/or system for quenching, dissipating,and/or otherwise resolving excited state energy may be configured andarranged to be disposable, serviceable, interchangeable, and/orreplaceable. These equivalents and alternatives along with obviouschanges and modifications are intended to be included within the scopeof the present disclosure. Accordingly, the foregoing disclosure isintended to be illustrative, but not limiting, of the scope of thedisclosure as illustrated by the appended claims.

The title, abstract, background, and headings are provided in compliancewith regulations and/or for the convenience of the reader. They includeno admissions as to the scope and content of prior art and nolimitations applicable to all disclosed embodiments.

EXAMPLES

Some specific example embodiments of the disclosure may be illustratedby one or more of the examples provided herein.

Example 1: Absorption Spectra

UV and visible light absorption spectra were recorded to investigate towhat extent each stabilizer itself absorbs UV light. FIG. 1 reveals thatthe stabilizers are strong UV absorbers with large extinctioncoefficients (molar absorptivity) of 16,200 M-1 cm-1 (Formula I(a)(1);λmax=334 nm) and 13,200 M-1 cm-1 (SolaStayS1; λmax=336 nm).Protoporphyrin IX has weak absorption bands above 450 nm, where the twocompounds are transparent (FIG. 2). The compound with the oxygen bridge(Formula II(d)(1)) caused a bathocromic shift of the UV absorption ofthe lowest energy band. The compound with the sulfur bridge (FormulaII(e)(1)) shifted the lowest energy band further into the visibleregion.

Example 2: Protoporphyrin Quenchers—Singlet State

Photoexcitation in these absorption bands generates singlet excitedstates which deactivate to the ground state or intersystem cross to thetriplet state. Formulas I, II, and/or III molecules and alkoxycrylenemay target the singlet excited states and/or the triplet states.

Fluorescence lifetime measurements are a convenient way to measuresinglet state quenching by stabilizers. Protoporphyrin IX decay traceswere recorded in the absence and presence of compound I(a)(1) and alkoxycrylene (FIG. 3). The experiments show that the compound of FormulaI(a)(1) significantly quenches the protoporphyrin IX fluorescence(reduces fluorescence lifetime; FIG. 3). However, the alkoxy crylenecompound caused no reduction in fluorescence lifetime, even at highconcentrations, such as 0.1 M (FIG. 3).

The collected data shown in FIG. 3 were used to determine thebimolecular quenching rate constant for singlet excited state quenchingby the compounds. The quenching rate constant may be directly extractedfrom the slope of the plot of the inverse fluorescence lifetime vs. theconcentration of the two compounds (FIG. 4). The data reveal a highquenching rate constant with the compound of Formulas I(a)(1), II(a)(1),II(d)(1), II(e)(1), and the mixture of II(b)(1) and II(c)(1) (close tothe diffusion limit) but no observable quenching with the alkoxy crylenecompound.

Example 3: Protoporphyrin Quenchers—Singlet State

To investigate if triplet states of protoporphyrin IX are quenched bythe two compounds, laser flash photolysis experiments were performed. Inthese experiments, a deoxygenated acetonitrile solution ofprotoporphyrin IX is excited with short laser pulses from a Nd-YAG laser(355 nm, 5 ns pulse width). Difference absorption kinetic traces wererecorded at different observation wavelengths (300 to 800 nm) and fromthese a transient absorption spectrum was constructed (FIG. 5A). Thisdifference spectrum shows ground state depletion at 400 nm (whereprotoporphyrin IX absorbs strongly; see FIG. 2). In addition, two bandsare observed at 320 and 440 nm, which are assigned to thetriplet-triplet absorption of protoporphyrin IX. The triplet absorptiondecayed with a lifetime of 52 μs with subsequent recovery of the groundstate absorption (FIG. 5B and FIG. 5C, respectively).

Triplet absorption kinetics at 440 nm may be utilized to obtain tripletquenching rate constants by the stabilizers. Triplet decay traces at 440nm were recorded in the presence of different amounts of the alkoxycrylene, Formulas I(a)(1), II(a)(1), II(d)(1), II(e)(1), and the mixtureof II(b)(1) and II(c)(1). The decay traces were fitted to a first-orderkinetics. The plot of these pseudo-first-order rate constants (inversedecay lifetime) vs. the concentration of the two compounds givesdirectly the bimolecular triplet quenching rate constant from the slope(FIG. 6).

The triplet quenching rate constant for the compound of Formula I(a)(1)is three orders of magnitude smaller than singlet excited statequenching by the compound of Formula I(a)(1). However, since the tripletlifetime (52 μs) is more than three orders of magnitude larger than thesinglet excited state lifetime (13 ns), the smaller rate constant fortriplet quenching is compensated by the longer triplet lifetime. Thismakes protoporphyrin IX triplet state quenching by the compound ofFormula I(a)(1) more efficient than singlet excited state quenching.Similar to the fluorescence quenching experiments, no triplet quenchingwas observed by the alkoxy crylene compound. Similarly, the tripletexcited state quenching of PPIX varies over three orders of magnitudefor Formula II(a)(1), II(d)(1), II(e) (1), and the mixture of II(b)(1)and II(c)(1). Interestingly, Formula II(a)(1) was the most efficientquencher—the PPIX triplet state quenching is almost as fast as thesinglet state quenching.

Because Formula II(a)(1) contains a ketone functionality, intersystemcrossing into the triplet state could be promoted after photoexcitationdue to spin-orbit coupling. Stabilizer triplet states could generatesinglet oxygen. Low-temperature luminescence experiments in a ethanolmatrix at 77 K were performed in search for phosphorescence of potentialtriplet states. Only a very weak luminescence was observed with maximumat 492 nm and a quantum yield of less than 1%. Because the excitationspectrum of this luminescence did not match the absorption spectrum, itcan be concluded that this luminescence is probably caused by animpurity and no long-lived triplet states of Formula II(a)(1) areformed.

Example 4: Mechanisms for Resolving Excited States—Control

The quenching mechanism of protoporphyrin IX singlet excited states andtriplet states by the compound of Formulas I, II, and III may be furtherclarified. A simple energy transfer mechanism would depend on thesinglet and triplet energies of compounds of Formula I andprotoporphyrin IX. To get information on excited state energies of thestabilizer, luminescence experiments were performed. The compound ofFormula I(a)(1) in ethanol solution did not give detectable fluorescenceat room temperature. However, weak luminescence was observed of thecompound of Formula I(a)(1) in a frozen ethanol matrix at 77 K. Theluminescence with maximum at 575 nm (FIG. 7c ) originates from thecompound of Formula I(a)(1), because the luminescence excitationspectrum (FIG. 7b ) matches well the absorption spectrum of the compoundof Formula I(a)(1) (FIG. 5a ). The luminescence lifetime could not bedetermined, because of the weak signal intensity. However, attempts torecord time resolved luminescence spectra suggests that the lifetime isshorter than the microsecond time scale. This suggests that theluminescence at 575 nm is not a typical phosphorescence and probably isthe fluorescence. If the luminescence at 575 nm is the fluorescence,then the Stoke's shift is unusually large. Independent of the assignmentof the luminescence to the fluorescence or phosphorescence, this excitedstate energy is higher than singlet and triplet energies ofprotoporphyrin IX and rules out a simple energy transfer quenchingmechanism. Another possible quenching mechanism is electron transferquenching which would depend on the redox potentials of theprotoporphyrin and the two quencher compounds.

Singlet oxygen quenching by compounds of Formula I is another possiblephotoprotection mechanism. A convenient way to generate singlet oxygenis by photoexcitation of tetraphenylporphyrin (TPP) in the presence ofdissolved oxygen. FIG. 8 shows a typical singlet oxygen phosphorescencespectrum (FIG. 8A) and its decay trace (FIG. 8B). The solvent CCl₄ wasselected, because it is known that the singlet oxygen has a longlifetime in this solvent (ms time scale), which makes the measurement ofquenching kinetics easier. Singlet oxygen phosphorescence decay traces,such as shown in FIG. 8B, were recorded in the presence of differentquencher concentrations. After fitting the decay traces to a first-orderkinetic model, the bimolecular quenching constants were determined fromthe plots shown in FIG. 9. The singlet oxygen quenching rate constantsof both compounds are relatively low. The slightly higher rate constantfor the alkoxy crylene compound is consistent with the additionalsubstituents compared to the compound of Formula I(a)(1).

Singlet oxygen was generated by pulsed laser excitation in the UV (355nm) by protoporphyrin IX. Protoporphyrin IX was selected on the basis ofits high extinction coefficient (FIG. 2). The solvent DMSO-d₆ wasselected because of good solubility of the sensitizer and stabilizers.The deuterated form of DMSO was used because of the longer singletoxygen lifetime in deuterated solvents compared to solvents containinghydrogen. FIG. 10 and FIG. 11 show kinetic traces of singlet oxygenphosphorescence generated from photoexcitation of protoporphyrin IX. Inthe presence of small amounts (250 μM) of the compound of FormulaI(a)(1) (FIG. 10) or the alkoxy crylene compound (FIG. 11) significantlyreduced singlet oxygen phosphorescence. However, the reduced amount ofgenerated singlet oxygen in the presence of the alkoxy cylene compoundis probably caused by competitive excitation light absorption, wheremost of the light is absorbed by the compound of Formula I(a)(1) or thetwo compounds and not by protoporphyrin IX. Excited state quenching ofthe protoporphyrin IX by the two compounds is unlikely to occur at theselow stabilizer concentrations (μM). As shown in FIGS. 4 and 6, muchhigher stabilizer concentrations are needed (mM) for excited sensitizerstate quenching of porphyrin compounds (sensitizers).

To investigate to what extent the stabilizers can generate singletoxygen upon direct UV photolysis, singlet oxygen phosphorescencemeasurements were performed under photolysis at 355 nm. For theseexperiments CCl₄ was selected as solvent, because of the long lifetimeof singlet oxygen in this solvent, which makes these experiments easierto perform. Weak singlet oxygen signals were observed upon photolysis at355 nm (FIG. 12). Using benzophenone as reference (quantum yield ofsinglet oxygen generation: 0.35) the low quantum yields of singletoxygen generation were estimated: compound of Formula I(a)(1): 0.015 andalkoxy crylene: ˜0.001.

To ensure that the observed weak singlet oxygen signals truly originatedfrom the two compounds and not from possible impurities in the sample orsolvent, singlet oxygen phosphorescence excitation spectra wererecorded. Because the excitation spectrum resembles the absorptionspectrum (FIG. 13), it can be concluded that the major amount ofobserved weak singlet oxygen phosphorescence was generated fromcompounds of Formula I. However, no match of the excitation spectrumwith the absorption spectrum was observed for the alkoxy crylenecompound, which suggests that the observed very weak singlet oxygenoriginated mostly from impurities.

In conclusion, the mechanism of photoprotection by compounds of FormulaI and the non-fused alkoxy crylene compound is probably dominated bytheir strong light absorption and fast deactivation to the ground state.However, excited state quenching, as shown for protoporphyn IX with thecompound of Formula I(a)(1), should provide additional photoprotection.

Example 5: Mechanisms for Resolving Excited States—Quenching

In the previous experiments, singlet oxygen was generated by pulsedlaser excitation in the UV spectral region (355 nm) of protoporphyroryIX. The singlet oxygen generation was mostly suppressed by addition ofsmall amounts of the compound of Formula I(a)(1) or the alkoxy crylenecompound (FIG. 14A and FIG. 14C). This was explained by a simple opticalscreening mechanism, where the compound of Formula I(a)(1) and alkoxycrylene absorb the UV light.

In this example, laser excitation was performed with visible light at532 nm, where the compound of Formula I(a)(1) and the alkoxy crylenecompound are transparent. No suppression of singlet oxygen generationwas observed by the presence of the alkoxy crylene compound even at highconcentrations (37 mM) (FIG. 1D). The absence of singlet oxygensuppression with 532 nm excitation supports the optical screeningmechanism with 355 nm excitation. In the presence of the compound ofFormula I(a)(1) at concentrations above 3 mM the amount of generatedsinglet oxygen was reduced (FIG. 14B). This reduction is probably causedby protoporphyrin IX excited state quenching by the compound of FormulaI(a)(1). In the previous experiments it was shown that protoporphyrin IXsinglet and triplet excited states are quenched by the compound ofFormula I(a)(1), but not by the alkoxy crylene compound.

The above-described experiments with protoporphyrin IX were performed inDMSO-d₆, a solvent with a relatively short singlet oxygen lifetime,because the polar protoporphyrin IX is not soluble enough is solventswith long singlet oxygen lifetimes, such as CDCl₃ and CCl₄. Solventswith long singlet oxygen lifetimes make singlet oxygen phosphorescencemeasurements significantly easier to perform. Additional experimentsusing the less polar dimethyl ester derivative of protoporphyrin IX wereperformed, which shows good solubility in CDCl₃. The excited stateproperties of protoporphyrin IX should not be affected by the methylester functionality.

Singlet oxygen phosphorescence experiments were performed to investigateif the large differences in triplet quenching rate constants have animpact on the observed singlet oxygen yields. The dimethyl esterderivative of PPIX (MePPIX, Formula IV(c)) was selected as sensitizer,because of better solubility in a solvent with long singlet oxygenlifetime (CDCl₃).

The excited state properties of protoporphyrin IX should not be effectedby the methyl ester functionality. Air saturated CDCl₃ of MePPIX wereexcited with a pulsed Nd-YAG laser with visible light at 532 nm, wherethe stabilizers are mostly transparent. FIG. 15 shows the generatedkinetic traces of singlet oxygen phosphorescence in the absence andpresence of stabilizers. Comparison of these kinetic traces shows majordifferences for the different stabilizers. The non-bridged stabilizer,alkoxy crylene did not suppress singlet oxygen generation. The lack ofsinglet oxygen suppression is consistent with the lack of observablequenching of singlet or triplet excited states of PPIX by alkoxycrylene. The bridged stabilizers suppressed singlet oxygen generation todifferent degrees with II(a)(1) showing the largest suppression.

The singlet oxygen phosphorescence experiments shown in FIG. 3 using thedimethyl ester derivative of protoporphyrin IX in CDCl₃ arequalitatively similar to those shown in FIG. 14 using protopophyrin IXin DMSO-d₆. Although singlet oxygen phosphorescence detection was easierin CDCl₃, decomposition of protoporphyrin IX dimethyl ester by singletoxygen caused a larger error in phosphorescence intensity, which wasespecially visible in FIG. 15D compared to FIG. 14D. The longer singletoxygen lifetime in CDCl₃ makes the chromophore more sensitive tooxidative damage.

To demonstrate that the suppression of singlet oxygen generation fromphotoexcitation at 532 nm is caused by singlet excited state quenchingof protoporphyrin IX by compounds of Formulas I, II, and III,Stern-Volmer analysis of the data in FIG. 14B and FIG. 15 was performed.The singlet oxygen phosphorescence intensity in the absence of thecompound of Formulas I(a)(1), II(a)(1), II(d)(1), II(e)(1), or a mixtureof II(b)(1) and II(c)(1) (I₀) divided by the singlet oxygenphosphorescence intensity in the presence of compounds of FormulaI/II(I) was plotted against the Formula I/II concentration (FIG. 16).From the slope of these plots (Stern-Volmer constant) and the lifetimeof the quenched excited state, the bimolecular quenching constant can beextracted. If the excited state, which is quenched by the compound ofFormula I(a)(1) (which causes a reduction in singlet oxygen production)is the singlet excited state of protoporphyrin IX then, using thepreviously measured fluorescence lifetime in acetonitrile (τf=12.7 ns) aquenching rate constant of 2.4×10⁹ M⁻¹ s⁻¹ is estimated. This rateconstant is in the same order of the previously measured rate constantusing fluorescence quenching (5.3×10⁹ M⁻¹ s⁻¹) which indicates thatsinglet excited state quenching of protoporphyrin by the compound ofFormula I(a)(1) is predominantly causing the suppression of singletoxygen generation. The rate constant derived from singlet oxygenphosphorescence quenching (FIG. 16) is only half of the more directlyderived rate constant from fluorescence quenching, which could be causedby the difference in solvents or by some contribution of protoporphyrintriplet quenching by the compound of Formula I(a)(1). If the suppressionof singlet oxygen generation would be entirely caused by tripletprotoporphyrin IX quenching by the compound of Formula I(a)(1), the rateconstant from the Stern-Volmer plot (FIG. 4) would be ˜3×10⁷ M⁻¹ s⁻¹considering a protoporphyrin IX triplet lifetime of ˜1 μs in airsaturated DMSO. This rate constant is 5 times higher than the directlymeasured rate constant by laser flash photolysis (6.1×10⁶ M⁻¹ s⁻¹). Thissuggests that protoporphyrin IX triplet quenching by compounds ofFormulas I, II, and III makes only a minor contribution to thesuppression of singlet oxygen generation under these conditions. It mustbe noted that protoporphyrin IX triplet lifetime of ˜1 μs in airsaturated DMSO was only estimated based on the directly measured tripletlifetime in air saturated acetonitrile and considering the differentoxygen concentration in DMSO compared to acetonitrile. If necessary, theprotoporphyrin IX triplet lifetime in air saturated DMSO can easily bemeasured by laser flash photolysis. The complex reaction mechanism issummarized in Scheme 1 (FIG. 17).

Additional cyano-containing fused tricyclic compounds having FormulasI(a)(1), II(a)(1), II(b)(1), II(c)(1), and II(d)(1) were tested againstthe alkoxy crylene compound as shown in FIG. 18.

The redox potential of protoporphyrin IX, Formulas I(a)(1), II(a)(1),II(b)(1), II(d)(1), II(e)(1), and alkoxy crylene were determined withrespect to a Ag/AgCl reference electrode. For these experiments,dimethylsulfoxide (DMSO) and tetrabutylammonium perchlorate (TBAP) wereobtained from Sigma Aldrich and used as received. Acetone was obtainedfrom Fisher Scientific. Solutions of 0.01 M (10 mM) of protoporphyrinIX, Formulas I(a)(1), II(a)(1), II(b)(1), II(d)(1), II(e)(1), and alkoxycrylene were prepared by dissolving measured amounts in a supportingelectrolyte of 0.1 M TBAP in DMSO; the total volume of each samplesolution was 15 mL. Platinum wires (BASi MW-1032) of diameter 0.5 mmwere employed for both the working electrode (WE) and counter electrode(CE). A dry-solvent tolerant Ag/AgCl reference electrode (RE) wasobtained from eDAQ (Model ET072). The WE and CE were cleaned prior toeach by first rinsing in acetone, then DI, followed by soaking in ˜50%aqueous H₂SO₄ for 10-20 minutes and then a final DI rinse. The REelectrode was cleaned prior to each use by an acetone rinse followed byDI rinse. Each sample solution was prepared in a fresh glass vial whichhad been rinsed with DI then acetone and allowed to dry Immediatelyafter preparing each solution, it was purged with pure N₂ gas for 15-20minutes with the electrodes in place. Voltammetry data was collectedshortly afterwards with an EG&G PAR 263 A Potentiostant/Galvanostatoperated using a Labview-based control program. Scans were performed atvarious potential ranges between +2.0V and −2.0V (vs Ag/AgCl); all scanrates were constant at 200 mV/s.

The voltammograms for protoporphyrin IX appear to show the presence oftwo distinct redox couples (FIG. 18A). The first redox couple (redcurve) has a large reduction peak at −1255 mV and a smaller oxidationpeak at −610 mV (two much smaller oxidation peaks are present at −202 mVand +164 mV which may also be associated with this couple); the redoxpotential for this couple is thus estimated as −932 mV. The second redoxcouple has a reduction peak near −1741 mV and an oxidation peak near−1152 mV; this yields a redox potential of approximately −1446 mV.

The voltammograms for Formula I(a)(1) also show the presence of twodistinct redox couples (FIG. 18B). The first redox couple (red curve)has a reduction peak at −757 mV and an oxidation peak at −560 mV; theredox potential for this couple is thus estimated as −658 mV. The secondredox couple has a reduction peak at −1297 mV and an oxidation peak at−1102 mV; the redox potential is approximately −1199 mV.

The voltammograms for Formula II(a)(1) show the presence of two distinctredox couples (FIG. 18C). The first redox couple (red curve) has areduction peak at −864 mV and an oxidation peak at −706 mV; the redoxpotential for this couple is thus estimated as −785 mV. The second redoxcouple has a reduction peak at −1537 mV and oxidation peaks at −1466 mV(small) and +430 mV (large); the redox potential is estimated as −1501mV.

The voltammograms for Formula II(e)(1) show the presence of two distinctredox couples (FIG. 18D). The first redox couple (red curve) has areduction peak at −969 mV and an oxidation peak at −782 mV; the redoxpotential for this couple is thus estimated as −875 mV. The second redoxcouple has a reduction peak at −1409 mV and oxidation peaks at −1286 mV(small) and +434 mV (large); the redox potential is estimated as −1347mV.

The voltammogram for Formula II(a)(1) shows the presence of only onedistinct redox couple (FIG. 18E). This couple has a reduction peak at−656 mV and an oxidation peak at −300 mV; the redox potential is thusestimated as −493 mV.

The voltammogram for Formula II(b)(1) also shows the presence of onlyone distinct redox couple (FIG. 18F). This couple has a reduction peakat −545 mV and an oxidation peak at +54 mV; the redox potential for thiscouple is thus estimated as −245 mV.

The voltammograms for alkoxy crylene show the presence of two distinctredox couples. The first redox couple (red curve) has a reduction peakat −1183 mV and an oxidation peak at −1038 mV; the redox potential forthis couple is thus estimated as −1110 mV. The second redox couple has areduction peak at −1751 mV and an oxidation peak at +318 mV; the redoxpotential is estimated as −694 mV.

Example 6: Stabilization of Avobenzone Compositions

Experiments were performed to assess the capacity of conjugated fusedpolycyclic molecules to photostabilize Avobenzone and the combination ofoxymethoxy cinnamate (OMC) and Avobenzone relative to ethylhexylmethoxycrylene. Example 6 compares cyano-containing fused tricycliccompounds at 3% (w/w) to photostabilize 3% Avobenzone, except for A6,which brings Y-1-22 up to the same molar concentration as the otherswhen they're at 3%. The results as shown in Table 1 are graphically inFIG. 19.

TABLE 1 Experiment 6-1, 20 uls solution on quartz Sample ID A1 A2 A3 A4A5 A6 A7 Ethylhexyl cyano 0.30 xanthenylidene acetate (Y-1-9) Ethylhexylcyano 0.30 thioxanthenylidene acetate (Y-1-15) Ethylhexyl dimethyl 0.300.45 2,2′-anthracene- 9,10-diylidenebis (cyanoacetate) (Y-1-22)Ethylhexyl 0.30 methoxycrylene ABP072707F 0.30 (a methoxy crylene)Avobenzone 0.30 0.30 0.30 0.30 0.30 0.30 0.30 PA 18 0.20 0.20 0.20 0.200.20 0.20 0.20 C12-C15 alkyl 2.00 1.70 1.70 1.70 1.70 1.55 1.70 benzoateEthyl acetate 7.50 7.50 7.50 7.50 7.50 7.50 7.50 Total 10.00 10.00 10.0010.00 10.00 10.00 10.00 % UVB remaining, 71.1 99.0 99.8 97.3 96.7 99.092.9 quartz, 10med % UVB remaining, 26.2 95.9 94.7 91.6 97.3 96.7 94.6quartz, 10med

Experiment 6-2 compares the compounds at 3% to photostabilize Avobenzoneat 3% and OMC at 7.5%. The results are shown in Table 2 and graphicallyin FIG. 20.

TABLE 2 Experiment 6-1, 20 uls solution on quartz Y-1-9 Y-1-15 Y-1-22SolaStay S1 ABP072707F % UVB 0.0 84.7 84.7 84.7 84.7 84.7 1.0 91.8 90.087.8 87.8 93.3 2.0 91.1 93.8 92.1 90.1 93.7 4.0 95.3 93.9 94.7 91.5 94.2% UVA 0.0 76.4 76.4 76.4 76.4 76.4 1.0 88.6 85.5 82.1 81.3 89.6 2.0 88.691.0 87.8 84.2 91.8 4.0 94.5 90.8 91.0 87.3 92.8 *SolaStay S1 -ethylhexyl methoxycrylene

Example 7: Synthesis of Compound II(d)(1)

A conjugated fused tricyclic molecule according to Formula II(d)(1) maybe synthesized as follows:

Xanthone (180 g, 0.9 mol) and methyl cyanoacetate (81 g, 1.0 equiv.)were dissolved in CH₂Cl₂ (2500 mL). TiCl₄ (180 mL) was first addeddropwise to the mixture while stirring, after the dripping, pyridine(120 mL) and CH₂Cl₂ (130 mL) were added dropwise slowly over a period of30 minutes with a gentle reflux, then the mixture was heated and stirredunder refluxing for 8 h. And then another 0.5 equiv. methyl cyanoacetate(54 g) was added to the mixture, another TiCl₄ (120 mL) and pyridine(100 mL) were added in turn, then the mixture was stirred underrefluxing (Monitored by TLC).

Then the mixture was treated with hydrochloric acid (10%, 1200 mL) andstirred sufficiently to transparent liquid. And then separated the oilphase, extracted the aqueous phase with CH₂Cl₂ (200 mL*3), combinedorganic phase.

The pure product was precipitated in 1500 mL methanol. The yield of thefinal product was 85%.

Example 8: Synthesis of Compound II(e)(1)

A conjugated fused tricyclic molecule according to Formula II(e)(1) maybe synthesized as follows:

Thioxanthen-9-one (53 g) was refluxed with SOCl₂ (250 mL), and then theexcess SOCl₂ was distilled. Excess methyl cyanoacetate (75 mL) was addedto the mixture. Then the mixture was stirred at 120° C. for 6 h. Thecrude product was purified by the column chromatography. The yield ofthe final product was 60%.

Example 9: Synthesis of Compound II(a)(1)

A conjugated fused tricyclic molecule according to Formula II(a)(1) maybe synthesized as follows:

A mixture of 160 g (0.80 mol) anthrone and 500 mL of thionyl chloridewas refluxed for 4 h, and then the excess SOCl₂ was distilled completelyunder reduced pressure. A solution of 180 g of methyl cyanoacetate in100 mL of dioxane was added timely. The solution was refluxed for anadditional 3 h and then cooled to 85° C., 800 mL of methanol was addedto the solution and stirred to room temperature. The brown solid wasfiltered and washed with methanol (300 mL). The crude product waspurified by active carbon decoloring in ethyl acetate. The yield of thefinal product was 61%.

Example 10: Synthesis of Compounds II(b)(1) and II(c)(1)

Conjugated fused tricyclic molecules according to Formula II(b)(1) andFormula II(c)(1) may be synthesized as follows:

Anthraquinone (260.8 g, 1.256 mol) and methyl cyanoacetate (320 g, 3.232mol, 2.57 equiv.) were dissolved in CH₂Cl₂ (3000 mL). TiCl₄ (400 mL) wasfirst added at room temperature, then a solution of pyridine (240 mL) inCH₂Cl₂ (400 mL) were added slowly over a period of 1 h, the dropwiseprocess without additional cooling measure and brought to a gentlereflux in the later stage. Then the mixture was heated and stirred atreflux for 2 h. Another 200 mL TiCl₄ and 120 mL pyridine were added tothe mixture in turn. Then the mixture was stirred under refluxing(Monitored by TLC).

Then the mixture was treated with hydrochloric acid (10%, 2000 mL) andstirred sufficiently to transparent liquid. And then separated the oilphase, extracted the aqueous phase with CH₂Cl₂ (200 mL*3), combinedorganic phase.

The pure product was precipitated in 1500 mL methanol. The yield of thefinal product was 95%.

Example 11: Synthesis of Compounds II(bg)(1) and II(bj)(1)

Conjugated fused tricyclic molecules according to Formula II(bg)(1) andFormula II(bj)(1) may be synthesized as follows:

Synthesis of Sulfoxide (II(bj)(1)

To a solution of Compound II(e)(1) in dichloromethane (0.7 M) at 0° C.was added meta-chloroperoxybenzoic acid (1.0 equivalent) and the mixturewas stirred for 30 min. The reaction mixture was washed with a saturatedaqueous solution of sodium bicarbonate and then extracted withdichloromethane. The organic layers were combined, dried over anhydrousmagnesium sulfate, filtered, and concentrated under vacuum. Purificationby column chromatography (Hexanes/Ethyl acetate) gave a white solid.Yield: 70%.

Synthesis of Sulfone (II(bg)(1)

To a solution of Formula II(e)(1) in dichloromethane (0.7 M) at 0° C.was added meta-chloroperoxybenzoic acid (2.0 equivalents). The solutionwas stirred at 0° C. for 30 min and then room temperature for 12 h. Thereaction mixture was washed with a saturated aqueous solution of sodiumbicarbonate and then extracted with dichloromethane. The organic layerswere combined, dried over anhydrous magnesium sulfate, filtered, andconcentrated under vacuum. Purification by recrystallization(dichloromethane) gave a white solid. Yield: 85%.

Example 12: Synthesis of Compounds I(b)(1)

A conjugated fused tricyclic molecule according to Formula I(b)(1) maybe synthesized as follows:

TiCl₄ (50 mL) in CCl₄ (100 mL) was added dropwise to the anhydrous THF(800 mL) in ice bath (<5° C.). The addition needed 0.5 h. Thenfluorenone (36 g, 0.2 mol) and dimethyl malonate (40 g, 0.3 mol) wasadded to the reaction mixture quickly and then stirred for 1 h (<5° C.).Then pyridine (64 mL) in anhydrous THF (150 mL) was added slowly to themixture for 1 h. The mixture was removed from the ice bath and refluxedfor 6 h. The progress of the reaction was monitored by TLC. Then themixture was treated with ice water (1 L) and extracted with EtOAc. Thecrude product was purified by recrystallization with ethanol (300 mL).The yield of the final product was 75%.

A conjugated fused tricyclic molecule according to Formula I(b)(2) maybe synthesized as follows:

TiCl₄ (60 mL) in CCl₄ (100 mL) was added dropwise to the anhydrous THF(1.3 L) in ice bath (<5° C.). The addition needed 0.5 h. Then fluorenone(36 g, 0.2 mol) and diisopropyl malonate (56.4 g, 0.3 mol) was added tothe reaction mixture quickly and then stirred for 1 h (<5° C.). Thenpyridine (50 mL) in anhydrous THF (250 mL) was added slowly to themixture for 1 h. The mixture was removed from the ice bath and refluxedfor 6 h. The progress of the reaction was monitored by TLC. Then themixture was treated with ice water (1 L) and extracted with EtOAc. Thecrude product was purified by recrystallization with ethanol (250 mL).The yield of the final product was 76%.

Example 13: Synthesis of Compound II(bl)(1)

A conjugated fused tricyclic molecule according to Formula II(bl)(1) maybe synthesized as follows:

Xanthone (49 g, 0.25 mol) was refluxed with SOCl₂ (250 mL), and then theexcess SOCl₂ was distilled. Excess dimethyl malonate (99 g, 0.75 mol)was added to the mixture. Then the mixture was stirred at 120° C. for 1h. The reaction mixture was cooled and added to 1 M NaOH (600 mL) icewater. The red solid was filtered and washed with water. The crudeproduct was purified by recrystallization with methanol (250 mL). Theyield of the final product was 56%.

A conjugated fused tricyclic molecule according to Formula II(f)(2) maybe synthesized as follows:

Xanthone (49 g, 0.25 mol) and DMF (1.5 mL) was refluxed with SOCl₂ (250mL), and then the excess SOCl₂ was distilled. Excess diisopropylmalonate (70 mL, 0.37 mol) was added to the mixture. Then the mixturewas stirred at 120° C. for 1 h. The reaction mixture was cooled andadded to 1 M NaOH (200 mL) ice water. The red solid was filtered andwashed with water. The crude product was purified by recrystallizationwith ethanol (200 mL). The yield of the final product was 70%.

Example 14: Performance Testing Compound II(a)(1)

A conjugated fused tricycle compound according to Formula II(a)(1)reduced visible light-induced free radicals in skin by up to 89% and didso in a dose-dependent manner (FIG. 21). The study was conducted usingpig skin, which is recognized for its similarity to human skin. Topicalapplication of aminolevulinic acid (ALA) induced the skin toover-produce the endogenous photosensitizer Protoporphyrin IX (PPIX).Solutions of Formula II(a)(1) at different concentrations were thentopically applied to the ALA treated skin after which it was exposed tobright green light. The resulting free radical content of the skin wasthen measured by Electron Spin Resonance (ESR). Studies conducted insolution have shown that Formula II(a)(1) suppresses singlet oxygenproduction by PPIX. This was the first study demonstrating suppressionof singlet oxygen in skin. Free radical reducing effects of the powerfulantioxidant Tocopherol (Vitamin E) were also under the same conditionsand found that Formula II(a)(1) is superior to Tocopherol in reducingvisible light-induced free radicals in ALA-treated skin. The mechanismsof action of Formula II(a)(1) and Tocopherol are different: the formerprevents free radicals from forming; the latter scavenges free radicalsafter they appear.

TABLE 3 Induced free radicals in pig skin treated with ALA and differentconcentrations of Formula II(a)(1) Concentration Formula II(a)(1) (mM)Free Radicals (a.u.) Free Radicals (%) 0 2506 ± 638 100   1.25 2311 ±331 92   2.5  1162 ± 225* 46 5  270 ± 88* 11 10   475 ± 212* 19Reference: 1% Tocopherol 1955 ± 366 78 *significant from the control (0mM Formula II(a)(1) at p < 0.05).

Example 15: Performance Testing Compound II(c)(1)

Assays were performed to evaluate the extent to which test compoundssuppress formation of reactive oxygen species (ROS) in cells.

A. Solubility in Cell Culture Media

All Conjugated fused polycyclic compounds tested (including FormulasII(a)(1), II(b)(1) and II(c)(1), and II(bk)) are highly soluble in DMSO,but poorly soluble in PBS buffer and cell culture medium. FormulasII(b)(1) and II(c)(1) can remain soluble in PBS buffer or cell culturemedium if its concentration is less 0.2 mM. At concentrations higherthan 0.2 mM, the solution begins to cloud and become emulsion like. Thisemulsion is able to remain stable for as long as 8 hours. Formula II(bk)is less soluble in PBS buffer and cell culture medium. It was onlyobserved to dissolve in PBS at concentrations of 0.1 mM or less. Similarto Formulas II(b)(1) and II(c)(1), increasing Formula II(bk)concentration above 0.1 mM results in a cloudy emulsion like solution.But this cloudy solution is fairly stable and can be kept for more than3 days. Formula II(a)(1) is especially difficult to dissolve in PBSbuffer. Concentrations as low as 0.05 mM, but even at such a lowconcentration, the solution was not observed to be stable for long. Onehour after adding Formula II(a)(1) to the PBS buffer or cell culturemedium, almost all Formula II(a)(1) precipitatde to the bottom of tubeor culture dish.

Conjugated fused polycyclic compounds may reduce the cellular ROS byquenching the excited states of PPIX. Accordingly, it may be desirableto deliver these molecules to and/or into cells where solubility maycorrelate with activity. Emulsification of conjugated fused polycycliccompounds may provide an effective delivery platform.

B. Toxicity

When HaCat cells, a human keratinocyte cell line, were treated withconjugated fused polycyclic compounds for short periods of time, therewas no observed toxicity. HaCat cells have been treated with FormulasII(b)(1) and II(c)(1) at concentrations of 0.4 mM, 0.8 mM and 1.6 mM forup to 8 hours. Formulas II(b)(1) and II(c)(1) were then removed from thecell culture medium and the cells were cultured in new medium foranother 24 hours. The treated cells were healthy, similar to the controlcells (no Formulas II(b)(1) and II(c)(1)treatment).

Toxicity was observed in some experiments over longer intervals.However, conjugated fused polycyclic compounds may be applied topicallyameliorating the potential for adverse impact. In addition, conjugatedfused polycyclic compounds may delivered as an emulsion and/or with oneor more additional molecules that lower observable toxicity.

C. Impact of Formulas II(b)(1) and II(c)(1) on Abundance of ROS

Conjugated fused polycyclic compounds may absorb UV light and, thereby,may screen, filter or block UV light (similar to sunscreen). The5-aminolevulinic acid (ALA) experiment described here was performed toassess the relative impact of such filtering on suppression of inducedcellular ROS. ALA is widely used in photodynamic therapy to kill tumorcells. It is a naturally occurring compound present in mammalian cellsthat can be metabolized to a porphyrin photosensitizer, protoporphyrinIX (PpIX). Applying ALA to the cells results in accumulation of PpIX inthe treated cells. Irradiating with red light (or green light) willactivate PpIX and lead to the production of cytotoxic reactive oxygenspecies (ROS).

HaCat cells were grown in 60 mm culture dishes to confluence. Confluentcells were treated with 8 mM ALA for 2 hour, then 2 mM of FormulasII(b)(1) and II(c)(1) was added (the control received an equal volume ofDMSO buffer without Conjugated fused polycyclic compound). After 1 hour,the cells were irradiated for 3 minutes with red light beam (630 nm).The negative control (no irradiation) samples were kept in darkness.After washing with PBS buffer, the cells were stained with DFFDA for 30minutes. The cells were washed with PBS 3 times again and then analyzedwith fluorescent microscopy.

As seen in FIGS. 22A-22C, ALA treatment and red light irradiationsignificantly boost the abundance of cellular ROS (compared to the “noirradiation” control cells). Cells contacted with 2 mM Formulas II(b)(1)and II(c)(1), displayed a marked reduction in cellular ROS—levelssimilar to the “no irradiation” normal cell control. FIG. 22D shows theresults of a quantitative analysis of the treated cells (n=4). ROS(based on relative fluorescence) for cells exposed to 8 mM ALA treatmentand 3 minutes of red light irradiation was 84.6% higher than ALAtreatment alone (no irradiation). On the other hand, cells incubatedwith 2 mM Formulas II(b)(1) and II(c)(1) for 1 hour, displayed a 15.85%increase in cellular ROS compared with the ALA treatment alone. Thatrepresents a more than 5 fold difference between the Formulas II(b)(1)and II(c)(1) treated and untreated cells. These data demonstrate thatthe Formulas II(b)(1) and II(c)(1) efficiently protect cells fromirradiation-induced increase in ROS, possibly by a mechanism other thansimple light filteration.

The dosage range of Formulas II(b)(1) and II(c)(1) was also analyzed. Asshown in FIG. 23, the cellular ROS (relative fluorescence) response isinversely correlated with to concentrations of Formulas II(b)(1) andII(c)(1) in the range of 0-0.2 mM (higher fluorescence at lowerconcentrations and lower fluorescence at higher concentrations). Theeffect of Formulas II(b)(1) and II(c)(1) on ROS appearance is saturatedwhen the concentration exceeds 0.2 mM. Formulas II(b)(1) and II(c)(1)are soluble in PBS buffer or cell culture medium at concentrations of0.2 mM and below, which may account for saturation of its effect onROS—concentrations of Formulas II(b)(1) and II(c)(1) over 0.2 mM may notresult in more molecules of Formulas II(b)(1) and II(c)(1) beingavailable to cells.

Next, impact on ROA appearance was assessed as a function of exposuretime. HaCat cells were seeded in the 60 mm cell culture dishes and grownto confluence. Confluent cells were treated with 8 mM ALA for 2 hours.Cells then received 1 mM of Formulas II(b)(1) and II(c)(1) and wereincubated for various time periods from 1 minute to 60 minutes. At theend of the respective incubation periods, cells were irradiated for 3minutes, washed with PBS buffer, and stained with DFFDA for 30 minutes.Cells were washed with PBS 3 times again and lysated by sonication. Celllysates were analyzed with fluorescent plate reader to assess thecellular ROS. Experiments were done in triplicate.

As illustrated in FIG. 24, a significant reduction in ROS abundance wasobserved upon incubating cells with Formulas II(b)(1) and II(c)(1) foras little as 1 minute. The maximum effect (reduction of ROS) wasobserved after a 10 minute incubation with 1 mM of Formulas II(b)(1) andII(c)(1).

D. Impact on ROS: Comparison of Formulas II(a)(1), II(b)(1), II(c)(1),and II(Bk)

HaCat cells were seeded in 96-well plates and grown to confluence.Confluent cells were treated with 8 mM ALA for 2 hours. Cells thenreceived 1 mM of Formula II(a)(1), II(b)(1)+II(c)(1), or II(bk).Following a one-hour incubation, cells were irradiated for 3 minutes,washed with PBS buffer, and stained with DFFDA for 30 minutes. Cellswere then washed with PBS and the plate was directly analyzed withfluorescent plate reader. Experiments were done 4 times.

Results shown in FIG. 25 indicate that of the molecules tested, FormulasII(b)(1) and II(c)(1) was the most effective at suppressing theaccumulation of cellular ROS after irradiation. As shown, with FormulasII(b)(1) and II(c)(1), the cellular ROS is close to baseline (noirradiation) after light irradiation. The ROS only increased by 7-12%.On the other hand, Formula II(a)(1) and Formula II(bk) are lessefficient. They confer some protection, but far less than FormulasII(b)(1) and II(c)(1). With Formula II(a)(1) and Formula II(bk), thecellular ROS increased 40 to 50% comparing to no irradiation. These arebetter than no conjugated fused polycyclics controls, in which ROSincreased by more than 60 to 70%, but not as good as Formulas II(b)(1)and II(c)(1).

E. Impact on Cell Viability: Comparison of Formulas II(a)(1), II(b)(1),II(c)(1), and II(Bk)

HaCat cells were seeded in 96-well plates and grown to confluence.Confluent cells were treated with 8 mM ALA for 2 hours. Cells thenreceived 1 mM of Formula II(a)(1), II(b)(1)+II(c)(1), or II(bk).Following a one-hour incubation, cells were irradiated for 3 minutes andimmediately washed with naïve cell culture media once. Additional cellculture media was added and the cells were cultured for 24 hours. A cellviabilty agent was added to each well and incubated for 2 hours. Cellviability was analyzed at the conclusion of this incubation by measuringthe fluorescence intensity (excitation/emission 560/590) of each well.Results shown in FIG. 26 indicate that control cells (without conjugatedfused polycyclic compound treatment) were almost completely killed byphototoxic ROS induced by ALA and light irradiation. Cell viability(cell metabolic activity) of light irradiated cells (without conjugatedfused polycyclic) was only 35% of normal cell control (no treatment).Cells treated with Formulas II(b)(1) and II(c)(1) were so healthy thatalmost no difference was observed relative to normal controls. About 50%of Formula II(a)(1) treated cells survived, while cells withoutconjugated fused polycyclic compound exposure and cells treated withII(bk) were almost 100% dead. As seen in FIG. 26, cells treated withFormulas II(b)(1) and II(c)(1) have relative cell viability of 96% (nosignificant different from normal cell control). The Formula II(a)(1)was also observed to protect cells from light irradiation induced injury(relative cell viability 61%). On the other hand, II(bk) has no observedeffect in protecting the cells (same as the samples without conjugatedfused polycyclic treatment, relative cell viability 36%).

To make sure that ALA and conjugated fused polycyclics treatmentsthemselves are not influencing cell viability, (or cause cellulartoxicity), dark toxicity analysis was performed. The experimentprocedures were exactly same as above for cell viability analysis exceptthat the red light irradiation step was omitted. As shown in FIG. 27,cells from all five treatments appeared healthy. No significantdifferent between the 5 groups of cells was observed other than FormulaII(a)(1) treatment showed a little toxicity.

Example 16: Performance Testing Formula II Compounds

The biomolecular quenching rate constants for singlet excited state(k_(q) ^(S)) and triplet excited state (k_(q) ^(T)) quenching of PPIX bystabilizers in acetonitrile solutions at room temperature is shown inTable 4, as well and the Stern-Volmer rate constants.

TABLE 4 Performance of Formula II Molecules Stern-Volmer Singlet TripletConstant of ¹O₂ Quenching Quenching Suppression Rate Constant RateConstant Formula (M⁻¹) (10⁹ M⁻¹s⁻¹) (10⁹ M⁻¹s⁻¹) Formula II(a)(1) 2405.2 3.2 Formula II(b)(1) + 31 4.5 0.25 II(c)(1) Formula I(a)(1) 30 5.30.0061 Formula II(d)(1) 27 3.7 0.14 Formula II(e)(1) 1.2 0.65 0.0012Negative Control 0.2 None None (alkoxy crylene)

Stern-Volmer constants are in direct correlation with the singlet oxygensuppression efficiency. Table 4 (above) summarizes the Stern-Volmerconstants and PPIX singlet and triplet state quenching rate constants.Three different ranges of Stern-Volmer constants were observed. Foralkoxy crylene and compound II(e)(1), only negligible singlet oxygensuppression and low Stern-Volmer constants were observed, which isprobably caused by the low PPIX singlet and triplet quenching rateconstants of these stabilizers. For compounds I(a)(1), II(d)(1), and themixture of II(b)(1) and II(c)(1), Stern-Volmer constants of about 30 M⁻¹were observed. For these three stabilizers, high PPIX singlet quenchingrate constants (about 5×10⁹ M⁻¹ s⁻¹) but low triplet quenching rateconstants (<10⁹ M⁻¹ s⁻¹) were observed. Here, the singlet oxygensuppression is probably dominated by PPIX singlet excited statequenching by these stabilizers. The highest Stern-Volmer constant wasobserved for compound II(a)(1) (240 M⁻¹). Because of the very high PPIXtriplet quenching rate constant by compound II(a)(1) (3.2×10⁹ M⁻¹ s⁻¹),the singlet oxygen suppression is probably dominated by tripletquenching. To prove this switch in mechanism and kinetic control ofsinglet oxygen suppression, additional kinetic parameters may bedetermined, which are easily accessible by laser flash photolysis andtime correlated single photon counting. These kinetic parameters mayinclude the MePPIX triplet and singlet lifetimes in air saturated andoxygen free CDCl₃ and the bimolecular quenching constant by oxygen.

What is claimed is:
 1. A method for resolving at least one excitedenergy state of a photoactive molecule, the method comprising:positioning the photoactive molecule in electrical communication with aconjugated fused polycyclic molecule prior to, during, or followingexcitation of the photoactive molecule to the at least one excitedenergy state, wherein the conjugated fused polycyclic molecule has astructure according to Formula III:

wherein m and n are each independently 0, 1, 2, 3, or 4, r and s eachmay be 0 or 1, A₃ and A₄ are each independently carbonyl, C═C(R₂₇)R₂₈,O, S, S═O, S(O)═O, or C═S, R₂₇ is independently nitrile, C(O)OR₂₉,C(O)R₃₀, C(O)N(R₃₁)R₃₂, C(O)—S—R₃₃, C(O)—O—S—R₃₄, C═CHR₃₅, N(R₃₆)₃ ⁺, F,Cl, Br, I, CF₃, CCl₃, NO₂, aryl, substituted aryl, or fused aryl, R₂₈ isindependently nitrile, C(O)OR₃₇, C(O)R₃₈, C(O)N(R₃₉)R₄₀, C(O)—S—R₄₁,C(O)—O—S—R₄₂, C═CHR₄₃, N(R₄₄)₃ ⁺, F, Cl, Br, I, CF₃, CCl₃, NO₂, aryl,substituted aryl, or fused aryl, R₂₉ and R₃₇ are each independently H,alkyl, branched alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl,substituted aryl, or fused aryl, R₃₀, R₃₁, R₃₂, R₃₃, R₃₄, R₃₅, R₃₈, R₃₉,R₄₀, R₄₁, R₄₂, and R₄₃ are each independently H, alkyl, cycloalkyl,alkenyl, cycloalkenyl, alkynyl, or aryl, substituted aryl, or fusedaryl, alkyl, substituted alkyl, or branched alkyl, R₃₆ and R₄₄ are eachindependently H or C₁-C₆ alkyl, and D₅ and D₆ are each independentlyR₂₇, R₂₈, heteroaryl, hydroxyl, alkyl, or alkoxyl, provided that r+s≧1,and at least one of A₃ and A₄ is C═C(R₂₇)R₂₈, wherein if r+s=1; then R₂₇and R₂₈ are each independently ≠F, Cl, Br, I, aryl, substituted aryl, orfused aryl; R₂₉ and R₃₇ are each independently ≠alkyl, branched alkyl,cycloalkyl, aryl, substituted aryl, or fused aryl; and D₅ and D₆ areeach independently ≠heteroaryl, hydroxyl, alkyl, or alkoxyl; and whereinif r+s=1, then only one of R₂₇ and R₂₈ is nitrile.
 2. A method accordingto claim 1, wherein the at least one excited state of the photoactivemolecule is resolved substantially without observable photochemicalreaction or without observable photosensitization reactions.
 3. A methodaccording to claim 1, wherein the at least one excited state of thephotoactive molecule is resolved substantially non-radiatively.
 4. Amethod according to claim 1, wherein the at least one excited state ofthe photoactive molecule is resolved substantially non-radiatively,substantially without observable photochemical reaction, andsubstantially without observable photosensitization reactions.